Magnocellular neurosecretory cells (MNCs) were impaled in perfused explants of rat hypothalamus. Evoked bursts of spikes were followed by an afterhyperpolarization (AHP) lasting 1-2 s. In each of 22 cells this AHP was selectively suppressed by low nanomolar concentrations of apamin (IC50 = 1.3 nM) or micromolar concentrations of d-tubocurarine (IC50 approximately 40 microM). Blockade of the AHP was accompanied by a decrease in spike accommodation and an unmasking of the late depolarizing afterpotential which induces burst firing in MNCs. Modulation of the Ca2+-dependent K+ (AHP) conductance by an endogenous apamin-like ligand could play an important role in the control of firing rate and pattern in MNCs.