Nonylphenol (NP) treatment of neonatal male rat pups decreased the size of their testes, epididymis, seminal vesicle, and ventral prostate, and increased the frequency of cryptorchidism (60.7%, n = 56 vs 0% in vehicle-treated control, n = 58) when examined at 31 d of age. NP effects are dose-dependent. These effects were only seen when NP was given at > or =20.8 mg/kg daily for 15 d. There is a critical period of vulnerability to NP during male reproductive development in the neonatal stage. Changes were found when NPs were given to male pups before 13 d of age, but not when given at > or =13 d of age. NP acts on the male reproductive tissues through the estrogen receptor (ER), since concomitant treatment with ICI 182,780, a specific ER antagonist, blocked NP's effects on the testis and male accessory organs. NP-treated males in the neonatal period had greatly reduced their subsequent capacity to impregnate young fertile females. Our results suggest that exposure of neonatal male rats to NP is potentially deleterious to their reproductive development and affects their reproductive performance.