4-tert-Octylphenol (OP) is a prevalent environmental pollutant which binds to estrogen receptors and exerts estrogenic actions in vitro. The effects of OP in vivo on mammalian female reproduction are not known. We investigated whether (i) exposure of neonatal rats to OP interfered with the onset of vaginal opening or their ability to have regular estrous cycles as adults and (ii) exposure of adult rats to OP interfered with estrous cyclicity and ovulation. Injection of 1 mg OP in corn oil sc on the day after birth did not affect the day of vaginal opening. However, 9 of 11 OP-treated rats were in persistent vaginal estrus when examined at three months after birth compared with 0 of 9 corn oil-injected controls, which cycled regularly. Ten of eleven neonatal rats injected with 1.7 mg of the estrogenic pesticide methoxychlor also were in persistent estrus at 3 months after birth, and all 10 neonatal rats injected with 1 mg of 2,4,5-trichlorophenol, which is apparently nonestrogenic, cycled regularly. Injection of 20 or 40 mg OP in corn oil vehicle sc three times weekly into previously untreated adult cyclic rats caused persistent estrus in 2 of 6 and 16 of 21 rats, respectively. Injections were continued for three more weeks in 5 of the 16 rats rendered persistent estrus by the 40 mg OP treatment. These rats remained in persistent estrus for the additional 3-week period. The other 11 persistent estrous rats in the 40 mg treatment group started to cycle regularly within 5-7 days after the last injection. Unlike pentobarbital, injection of OP into cyclic rats during the afternoon of proestrus did not block ovulation. These results provide strong evidence that OP acts like estrogen in vivo in both neonatal and adult female rats to exert effects that block reproductive cyclicity.