The effects of delta 9-tetrahydrocannabinol (delta 9-THC) on endocrine responses of ovariectomized rats and intact male rats were investigated. In delta 9-THC treated ovariectomized rats, the mediobasal hypothalamic (MBH) LHRH and methionine-enkephalin (met-enk) contents were high compared to either vehicle or naloxone groups. However, delta 9-THC, when administered simultaneously with naloxone, failed to change MBH LHRH levels in the ovariectomized rats. This suggests that LHRH release from the MBH, which is normally accelerated by ovariectomy, is blocked by delta 9-THC and this inhibitory effect of delta 9-THC on LHRH release is reversed by naloxone, suggesting an involvement of endogenous opiate system. In a second experiment using intact male rats, delta 9-THC was administered at 2 mg, 15 mg, and 30 mg/kg body weight. The delta 9-THC decreased immunoassayable LHRH in anterior hypothalamus preoptic area (AHPOA) and MBH in a dose-related manner. Significant increases in serum corticosterone and decreases in serum testosterone were also observed in the rats due to delta 9-THC treatment. The met-enk content of AHPOA and MBH was significantly increased in delta 9-treated rats. The results of this study suggest that delta 9-THC may decrease biosynthesis and/or release of LHRH by partly interacting with the endogenous opiate system.