In order to study the involvement of the brain histamine system on the sexual behavior of rats prenatally exposed to the histamine H1 receptor blockader, diphenhydramine (DPD), the female lordotic response and male sexual behavior were analyzed. The results show that the lordotic response in the prenatal DPD-treated rats was increased in relation to control animals. Impairment of male sexual behavior was indicated by an increase in ejaculation latency, in the number of mounts and a decrease in the number of ejaculations up to 30 min after the first intromission. Prenatal exposure to DPD thus appears to alter female and male sexual behavior on reaching adulthood.