There is increasing concern about the potential teratogenic effects of caffeine. Laboratory rodents were widely used for the teratological evaluation of caffeine. However, few studies have been carried out in non-mammalian organisms. Caffeine, dissolved in sterile water, was injected into the air sacs of fertile White Leghorn chick eggs at doses of 100, 200, 300, 400, 500, 700, 900, and 1,100 micrograms per egg. Control eggs were injected with an equivalent volume of sterile water (0.1 ml/egg). The embryos were treated at either 48, 72, or 96 hours incubation. On day 9, live embryos were recovered and examined for external malformations after staging and weighing. Treatment with 400 and 1,100 micrograms caffeine at 48 hours incubation resulted in a significantly high incidence of abnormal embryos, compared to the controls. The most common malformations included reduced body, microphthalmia, exencephaly, everted viscera and short neck. A significant number of embryos died following treatment with 1,100 micrograms caffeine at 48 hours incubation, and 400 and 700 micrograms at 72 hours incubation. Embryonic growth was not affected. Even though it is not possible to extrapolate these findings directly to humans, moderation in the consumption of caffeine-containing beverages during pregnancy is recommended.