Enrichment of hepatoma cells with arachidonic acid increases fluidity of plasma membranes, unstimulated lipid peroxidation and basal adenylate cyclase activity, whereas enrichment with stearic acid decreases fluidity and does not cause any variation in lipid peroxidation or adenylate cyclase. The increase in adenylate cyclase activity may be due to the increase not only in fluidity, but also in lipid peroxidation products. Indeed, adenylate cyclase is stimulated by 4-hydroxynonenal, one important product of lipid peroxidation, when added to plasma membranes. 4-hydroxynonenal increases adenylate cyclase two-fold in unenriched plasma membranes and three-fold in plasma membranes enriched with arachidonic acid in comparison with basal activity.