A case-control study was conducted to assess maternal hormonal factors associated with increased risk of bearing a cryptorchid son. Serum samples were collected during the first trimester of pregnancy from participants in the US Collaborative Perinatal Study. Twenty-five mothers of normal offspring (controls) were individually matched on medical center, age, parity, weight and length of gestation at the time of sampling to women bearing sons who had a diagnosis of cryptorchidism at one year of age or older. Compared with controls, mothers of cryptorchid sons (cases) had significantly greater percentages of non-protein bound (P = 0.010) and albumin-bound (P = 0.014) estradiol during the first trimester of the index pregnancy. On average, cases had 16% more bioavailable oestradiol than controls. Levels of human chorionic gonadotropin, testosterone, non-protein bound testosterone and sex-hormone binding globulin did not differ between the two groups. The data presented support the hypothesis that cryptorchidism results from elevated maternal oestrogen levels early in pregnancy.