Providing squids--especially their giant axons--for biomedical research has now been achieved in 10 mariculture trials extending through multiple generations. The noteworthy biological characteristics of Sepioteuthis lessoniana are (1) this species is behaviorally and morphologically well suited to the laboratory environment; (2) the life cycle is completed in 4-6 months; (3) growth is rapid (12% and 5% wet body weight d-1 for 100 d and for the life span, respectively), with adult size ranging from 0.4-2.2 kg; (4) feeding rates are high (30% wet body weight d-1), and a variety of live crustaceans and fishes are eaten; (5) crowding is tolerated (about 4 squids m-3); (6) the incidence of disease and cannibalism is low; and (7) reproduction in captivity allows culture through three successive generations. Engineering factors contributed to culture success: (1) physical design (i.e., size, shape, and painted pattern) of the culture tanks; (2) patterns of water flow in the culture tanks; (3) water filtration systems; and (4) spawning substrates. Initial production (a few hundred squids per year) suggests that large-scale culture will be able to supply the needs of the biomedical research community. The size (> 400 microns in diameter) and characteristics of the giant axons of Sepioteuthis are appropriate for experimentation, and other studies indicate that the eye, oculomotor/equilibrium system, olfactory system, blood, and ink are equally suitable for research.