We have tested the hypothesis that maternal exposure to octylphenol, a putative endocrine disrupting chemical, will suppress gonadotropin secretion with a concomitant decrease in testis size and Sertoli cell number during fetal life in the lamb. In Exp 1, pregnant ewes received a continuous iv infusion of diethylstilbestrol (DES; 50 microg/kg x day), octylphenol (1000 microg/kg x day), or vehicle (1:4, alcohol-saline) from days 110-115 of gestation. The fetuses were chronically catheterized in utero, and blood samples were collected every 8 h to monitor gonadotropin secretion. In Exp 2, pregnant ewes received twice weekly sc injections of DES (0.5 microg/kg x day), octylphenol (1000 microg/kg x day), or corn oil from day 70 of gestation to birth. The pituitary gland and testes were collected from the lambs at the end of the treatment period. In Exp 1, maternal exposure to octylphenol suppressed (P < 0.05) FSH concentrations without any effect (P > 0.05) on LH concentrations compared with those in control fetuses. In Exp 2, long-term maternal exposure to octylphenol or a 1000-fold lower dose of DES suppressed (P < 0.05) FSH, messenger RNA levels and the number of FSHbeta-immunopositive cells in the pituitary gland and reduced testis weight and the number of Sertoli cells in the testis compared with those in control lambs. We conclude that maternal exposure to octylphenol inhibits the secretion of FSH in the fetus with a concomitant decrease in testis size and Sertoli cell number at birth.