Identified cells in Aplysia (R15, R2, LPG) and cell 11 in Otala have been used to investigate the effects of divalent cations, temperature, pH and ouabain on neuronal activity. Divalent cations act primarily to regulate the appearance of bursting pacemaker potential (BPP) activity in these cells. These ions are necessary for B generation and will inhibit its appearance at high concentrations (Ca greater than Mg greater that greater than Sr). In addition, Ca is involved in the seasonal modulation of BPP activity in a neurosecretory cell in Otala. Monovalent cations play secondary roles as regulators of BPP activity by competing with divalent cations for the sites involved in the regulation of the (probable) monovalent conductances underlying BPPs. The effects of pH, temperature and ouabain on membrane properties and BPP activity are partly related to their interaction with divalent cations. The results described indicate important roles for divalent cations in the regulation of the expression of BPP activity and its underlying membrane properties both in different nerve cells and in the same cell during dormancy and activity of the snails.