1. In response to brief stimulation of an afferent input the bag cell neurons of Aplysia depolarize by 15-20 mV and generate an afterdischarge that, in vitro, lasts for approximately 30 min. During the discharge these neurons secrete three small peptides [bag cell peptides (BCPs)], Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu (alpha-BCP), Arg-Leu-Arg-Phe-His (beta-BCP), and Arg-Leu-Arg-Phe-Asp (gamma-BCP), that share a common core sequence and that have electrophysiological effects on the bag cell neurons themselves. We have now studied the action of these three peptides on bag cell neurons isolated in culture. All three peptides were found to be capable of producing a depolarization of these cells. 2. The ability of alpha-, beta-, and gamma-BCP to induce a depolarization in isolated bag cell neurons exhibits a seasonal variability. The response to the peptides is maximal from early summer through late fall and parallels the frequency of egg-laying in vivo. 3. The depolarization induced by alpha-, beta-, and gamma-BCP desensitizes with repeated application of peptide. Desensitization of the response to one peptide does not, however, prevent the response to application of one of the other two peptides. This suggests that separate autoreceptor populations exist for alpha-, beta-, and gamma-BCP. 4. As reported previously, desensitization of the depolarizing response to the peptides was also observed after preincubation of intact clusters of bag cell neurons with a high concentration of all three peptides.(ABSTRACT TRUNCATED AT 250 WORDS)