Epidemiological variables in relation to hypospadias were analyzed in a case-control study of a liveborn population from six Latin American countries. the frequency of hypospadias was 7.6 per 10,000 livebirths (324/423,839). The cases were divided into three types: distal (72%), proximal (18.5%) and non-specified cases (9.5%). The control group consisted of the first nonmalformed child born after each of the patients and was matched by sex, place, and time of birth. Other coexisting malformations were found in 13.6% of cases. The Brazilian sample showed the highest incidence rate (17.7/10,00) and also the highest incidence of severe forms (5.0/10,000) as compared with the other countries. a circannual rhythm was detected using several different statistical procedures. Low mean birth weight, twinning, vaginal bleeding, and drug exposure during the 1st trimester (particularly sex hormones) were found to be risk factors. The more severe forms had a higher neonatal mortality rate and higher inbreeding when compared with the controls or milder forms. The heritability coefficient was 0.6772 +/- 0.0675. The possible role of maternal sex hormone intake and disturbances of human chorionic gonadotropin during the first trimester are discussed.