While recent evidence indicates a role for serotonin (5-HT) in modulating the defensive tail-withdrawal reflex in Aplysia, little information exists concerning the specificity of these 5-HT effects. As a first-step in addressing this issue we have examined the dose-response relationship for one aspect of the 5-HT modulation (enhancement of cAMP levels in isolated clusters of sensory neurons) and compared the effects of 5-HT with three potential neurotransmitters: tryptamine, FMRFamide (Phe-Met-Arg-Phe-NH2) and small cardioactive peptideB (SCPB). Cyclic adenosine monophosphate (cAMP) levels were enhanced as a graded function of the concentration of 5-HT with an EC50 of 14 microM. At a concentration of 5 microM, both 5-HT and SCPB produced nearly identical increases in the cAMP content of sensory neurons. In contrast, 5 microM tryptamine or 5 microM FMRFamide had little or no effect on cAMP levels. We also examined the effects of these agents on membrane currents and membrane conductance. Both 5-HT and SCPB produced an inward current associated with a decrease in input conductance. Tryptamine had little or no effect, while FMRFamide produced a response opposite to that of 5-HT and SCPB; an outward current associated with an increase in membrane conductance.