Although the peptidergic bag cell neurons of Aplysia are ordinarily silent, they respond to brief electrical stimulation by producing an afterdischarge of about 30 min duration. This afterdischarge is followed by a refractory period lasting many hours during which electrical stimulation either fails to initiate afterdischarges or produces discharges of much shorter duration. Previous work has demonstrated that cyclic AMP plays a role in the genesis of afterdischarge, both in intact bag cell clusters and in isolated cultured bag cells. We have now examined the hypothesis that in the refractory period either the synthesis of cyclic AMP or the response to cyclic AMP is attenuated. Direct measurements of cyclic AMP showed that cyclic AMP levels in the bag cell neurons are elevated to a similar extent after stimulation in refractory and nonrefractory clusters of neurons. We have found, however, that the response to cyclic AMP is altered during the refractory period. The electrophysiological responses of bag cell neurons were first examined in intact clusters of cells within the abdominal ganglion. Cyclic AMP levels were elevated using the adenylate cyclase activator, forskolin, in the presence of theophylline (FT). The duration of a first bag cell afterdischarge could be greatly increased if FT was added before stimulation. The duration of a stimulated second bag cell afterdischarge could also be significantly increased if FT was added within a brief period following the end of the first afterdischarge. Furthermore, at these times the addition of FT often resulted in the onset of spontaneous afterdischarges.(ABSTRACT TRUNCATED AT 250 WORDS)