In previous study the major psychoactive ingredient of marihuana (Δ1-THC) has been shown to inhibit ovarian prostaglandin synthesis when administered to normally cycling rats in the early afternoon of proestrus. These results suggested a direct suppressive effect of the drug on the ovary. The purpose of this study was to evaluate the effect of Δ1-THC on steroidogenesis in granulosa cells (GC) in vitro. Incubation of GC with Δ1-THC (10–50 µM) effectively inhibited LH-stimulatable progestin production. This suppressive effect was not abolished by washing the cells after 24 h of culture in the presence of Δ1-THC, indicating the irreversible nature of the blocking effect of Δ1-THC. By contrast, estradiol production following incubation of GC with testosterone (1 µg/ml) was not inhibited by similar concentrations of Δ1-THC, thus suggesting that △1-THC does not inhibit aromatase activity in GC. In addition, Δ1-THC was shown to inhibit cAMP production as well as 125I-hCG binding capacity to GC. Administration of 8-Br-cAMP did not abolish the Δ1-THC-induced block, suggesting that the drug probably acts distal to the cAMP s