Evidence suggests that the serotonin 5HT-1 receptor site is functionally linked to adenylate cyclase in the brain, but a biochemical effector system which is linked to the serotonin 5HT-2 receptor site has not been found. In the present paper we report an investigation of 5HT stimulated phosphatidylinositol (PI) hydrolysis in rat cerebral cortex and have found that selective 5HT-2 antagonists (pizotifen and ketanserin) block 5HT's effect upon PI metabolism. These data suggest that 5HT stimulated PI hydrolysis is mediated by the 5HT-2 binding site.