We examined the effect of the voltage-sensitive Ca2+ channel antagonists, diltiazem and nifedipine, on basal and stimulated growth hormone (GH) release from purified somatotrophs. Our aim was to ascertain whether an influx of Ca2+ from the extracellular to the intracellular compartment is essential for augmented release. Basal release was decreased in a concentration-dependent manner by both diltiazem and nifedipine, while cAMP accumulation was unaffected. The release of GH induced by 29 mM K+ was blocked by diltiazem and nifedipine, at 10(-7) and 10(-8) M, respectively. Again cAMP was unaffected. The release of GH induced by growth hormone-releasing factor was significantly reduced by 10(-4) M diltiazem and completely blocked by nifedipine at a concentration of 10(-6) M or greater. Where the antagonists were effective, the growth hormone-releasing factor induced increase in cAMP accumulation was augmented. We conclude that an influx of Ca2+ from the extracellular compartment is essential for stimulated GH release.