Recent evidence suggests that serotonin (5-HT) and a neuropeptide, small cardioactive peptideB (SCPB), exert parallel modulatory actions on neuronal and muscular function in Aplysia via changes in the levels of cAMP. We have examined the effects of both of these neurotransmitters on the adenylate cyclase activity in membrane homogenates of pleural ganglia. The results indicated that 5-HT and SCPB enhance the production of cAMP via a direct activation of adenylate cyclase. In addition, we found that the increase in cyclase activity produced by 5-HT could be selectively blocked by the S2-serotonergic antagonists, ketanserin and ritanserin. Thus, specific 5-HT receptors are present which appear to be distinct from those that mediate the effects of SCPB on the activity of adenylate cyclase.