We investigated the influence of calcium ions on the secretion of anterior pituitary hormones basally and in response to exogenous hypothalamic releasing factors in 6 men with pituitary tumors. To this end, concentrations of LH, FSH, TSH, growth hormone and prolactin were measured in blood collected at 10-min intervals basally and during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min). Study sessions were randomized to iv saline, calcium, or diltiazem infusions or oral diltiazem administration. Our results indicate that in contrast to responses in normal men, iv calcium injections do not suppress circulating prolactin concentrations in patients with prolactin-secreting pituitary tumors. Moreover, neither oral diltiazem administration for one week nor acute iv diltiazem infusion suppressed the hyperprolactinemia of tumor patients. However, there were significant effects of drug and calcium treatments on serum concentrations of FSH, GH and testosterone, but not LH or TSH. Moreover, during GnRH-TRH stimulation, there were significant differences in LH, TSH, and testosterone responses in tumor patients compared to normal men. In summary, iv calcium infusion was associated with invariant basal release of anterior pituitary tumoral hormones in patients with pituitary adenomas. However, there were significant differences in the GnRH/TRH-stimulated release of certain anterior pituitary hormones in tumor patients compared to normal men in response to iv calcium and the calcium-channel antagonist, diltiazem.