The adverse effect of therapeutic use of sex hormones during pregnancy inducing pseudohermaphroditism in female offspring has been well known since the early 1950s. Consequently there has been great concern about the potential effects on the offspring of women who use these agents during gestation. Some studies have reported an association, particularly of oral contraceptives used during pregnancy, with specific types of congenital defects, while this was not observed in other studies. Here we present the results of a large case-control study on the effect of prenatal exposure to each type of sex hormone. Cases were those malformed infants of unknown cause, that is, excluding syndromes and those cases with defects that have dominant or recessive inheritance, and those due to recognized teratogens. The controls were selected from the same population as the cases and are representative of those who, had they developed malformations, would have been selected as cases. The results, after controlling potential cofounder factors with different logistic regression analyses, do not support the hypothesis that prenatal exposure to sex hormones increases the risk of genital and nongenital malformations.