The crew of the red seal ships were international, for many Chinese, Portuguese, and Dutch pilots and interpreters joined the sails. The first Red Seal ships were required to have a Portuguese pilot on board, although the Japanese progressively developed pilots of their own. The Portolan maps used on the Red Seal ships were drawn on the Portuguese model, with directions in the Japanese language.
Major Southeast Asian ports, including Spanish Manila, Vietnamese Hoi An, Siamese Ayutthaya, Malay Pattani, welcomed the Japanese merchant ships, and many Japanese settled in these ports, forming small Japanese enclaves.
The Japanese seem to have been feared throughout Asian countries, according to a contemporary, Sir Edward Michelbourne:
The Japons are not suffered to land in any port in India (Asia) with weapons; being accounted a people so desperate and daring, that they are feared in all places where they come.
A Dutch commander wrote (circa 1615): "they are a rough and a fearless people, lambs in their own country, but well-nigh devils outside of it".
Around 50 Red Seal ships to Luzon in the Philippines are recorded between 1604 and 1624 (and only 4 more recorded by 1635). The Japanese had established quite early an enclave at Dilao, a suburb of Manila, where they numbered between 300 to 400 in 1593. In 1603, during the Sangley rebellion, they numbered 1,500 and 3,000 in 1606. The Franciscan friar Luis Sotelo was involved in the support of the Dilao enclave between 1600 and 1608.
The Japanese led an abortive rebellion in Dilao against the Spanish in 1606-1607. Their numbers rose again with the interdiction of Christianity by Tokugawa Ieyasu in 1614, when 300 Japanese Christian refugees under Takayama Ukon settled in the Philippines. They are at the origin of today's 200,000-strong Japanese population in the Philippines.
Around 56 Red Seal ships to Siam are recorded between 1604 and 1635. The Japanese community in Siam seems to have been in the hundreds, as described by Padre Antonio Francisco Cardim, who recounted having administered sacrament to around 400 Japanese Christians in 1627 in the Thai capital of Ayuthaya ("a 400 japoes christaos") (Ishii Yoneo, Multicultural Japan).
In December 1605, John Davis, the famous English explorer, was killed by Japanese pirates off the coast of Siam, thus becoming the first Englishman to be killed by a Japanese.
The colony was active in trade, particularly in the export of deer-hide and sappan wood to Japan in exchange for Japanese silver and Japanese handicrafts (swords, lacquered boxes, high-quality papers). They were noted by the Dutch for challenging the trade monopoly of the Dutch East India Company (VOC), as their strong position with the King of Siam typically allowed them to buy at least 50% of the total production, leaving small quantities of a lesser quality to other traders.
A Japanese adventurer, Yamada Nagamasa, became very influential and ruled part of the kingdom of Siam (Thailand) during that period. The colony also had an important military role in Thailand.
Although prohibited by China from touching Chinese soil, Japanese sailors from Red Seal ships transited through Macau in some numbers. In November 1608, a fight between about 100 Japanese samurai, wielding katana and muskets, and Portuguese soldiers under the acting governor and Captain of the Japan voyage André Pessoa led to a fight in which 50 Japanese lost their lives. The remaining 50 were released by the authorities after having to sign an affidavit blaming themselves for the incident. Ieyasu prohibited visits to Macau by Japanese nationals in 1609:
Since it is an undoubted fact that the going of Japanese in ships to Macau is prejudicial to that place, this practice will be strictly prohibited for the future. (July 25, 1609, Ieyasu Shuinjo, remitted to Mateo Leitão)
Although few Red Seal Ships are recorded for the areas of modern Indonesia (Java, Spice Islands), possibly because of the remoteness and because of the direct Dutch involvement there, Japanese samurai were recruited by the Dutch in the area. They distinguished themselves in the capture of the Banda Islands from the English and the defense of Batavia, until the practice of hiring Japanese mercenaries was prohibited by the Shogun in 1621. In 1618, Coen, the Dutch governor of Java, requested 25 Japanese Samurai to be sent to him from Japan. In 1620, the Dutch record that 90 Japanese samurai were recruited from the islands surrounding Java, in order to reinforce the fort of Batavia.
In 1623, during the Amboyna massacre, 9 Japanese mercenaries were recorded to have been with the 10 English traders of the British East India Company factory. They were tortured and killed by Dutch forces from the neighbouring factory. This event was partly the cause for the advent of the Anglo-Dutch Wars.
The Japanese adventurer Tenjiku "Indie" Tokubei is related to have travelled to Siam as well as India onboard a Red Seal ship with Jan Joosten. Upon his return to Japan, Tokubei wrote an essay titled "Tenjiku Tōkai Monogatari" (Relations of travels to India) on his adventures in foreign countries, which became very popular in Japan. He is sometimes referred to as the Marco Polo of Japan.
Other major destinations included Cochinchina (74 ships), Cambodia (44 ships), Taiwan (35 ships), and Annam in Vietnam (14 ships).