1. Spontaneous discharge of action potentials (Na spikes) in cells isolated from rat pars intermedia was slowed or arrested by Co(2+), Ni(2+) or Mn(2+), which block voltage-dependent Ca channels in these cells. The amplitude of persisting spikes was undiminished. The effects resembled those of dopamine.2. Action potential frequency decreased when the Ca(2+) concentration was lowered to 0.1 mM and increased when the Ca(2+) concentration was raised from this level to 1 mM or 2 mM or when Ba(2+) (2 mM) was introduced. These effects, together with those of Co(2+), Ni(2+) and Mn(2+), are consistent with the possibility that Ca(2+) participates in the regulation of spike discharge.3. Verapamil, methoxyverapamil (D600), and nifedipine reduced the amplitude of the individual Na spikes in concentrations that had little effect on voltage-dependent Ca channels. Action potential frequency was comparatively little affected by these drugs.4. K(+) (15 mM) stimulated action potential frequency and this effect too was suppressed by dopamine or Co(2+).5. The effect which dopamine had of slowing spontaneous discharge, like the inhibitory effect on secretion, was blocked by metoclopramide. But otherwise the mechanism is unclear: dopamine blocked voltage-dependent Ca channels in some cells but not in most others.6. The effects of K(+) and Ba(2+) of eliciting spikes, the suppression of Na-spike discharge by Co(2+) and related Ca-channel blocking cations, and the unspecific effects of the organic ;Ca channel blockers', all have implications for the use of these substances as tools to analyse stimulus-secretion coupling.