Vitamin A, a known teratogen of the central nervous system, was administered in various doses, at the time of active neural tube closure, to pregnant curly-tail mice which have a genetic predisposition to neural tube defects (n.t.d.), and to A Strong mice, which are not so predisposed. The curly-tail mice showed an enhanced susceptibility to the teratogenic effect of vitamin A given on day 8 of gestation, demonstrating a clear gene--environment interaction. There was a differential response by the two sexes. Females seemed to be more affected by the vitamin A than males. When vitamin A was administered on day 9, instead of day 8, of gestation, the incidence of n.t.d. decreased rather than increased. Furthermore, the number of mice affected by n.t.d. was markedly lower even than that found spontaneously in untreated curly-tail mice.