The phospholipases controlling the release of arachidonic acid in mouse peritoneal macrophages have been shown to be stimulated by the natural psychoactive cannabinoids. A close correlation was observed between the potencies of these substances in elevating arachidonate levels in vitro and the reported activities in a behavioral assay in monkeys and in producing a “high” in humans. The order of activity with the macrophages was Δ 1-tetrahydrocannabinol ( Δ 1-THC) > 7-OH- Δ 1-THC > 6 α-OH- Δ 1-THC > 6 β- Δ 1-THC ⪢ Δ 6-THC-7-oic acid. It is suggested that this effect, which has now been shown in several diverse cell types, may serve as a model for studying the mechanism of action of THC.