In previous study the major psychoactive ingredient of marihuana (Δ<sup>1</sup>-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 Δ<sup>1</sup>-THC on steroidogenesis in granulosa cells (GC) in vitro. Incubation of GC with Δ<sup>1</sup>-THC (10–50 µ M) 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 Δ<sup>1</sup>-THC, indicating the irreversible nature of the blocking effect of Δ<sup>1</sup>-THC. By contrast, estradiol production following incubation of GC with testosterone (1 µg/ml) was not inhibited by similar concentrations of Δ<sup>1</sup>-THC, thus suggesting that △<sup>1</sup>-THC does not inhibit aromatase activity in GC. In addition, Δ<sup>1</sup>-THC was shown to inhibit cAMP production as well as <sup>125</sup>I-hCG binding capacity to GC. Administration of 8-Br-cAMP did not abolish the Δ<sup>1</sup>-THC-induced block, suggesting that the drug probably acts distal to the cAMP site of action.