Several authors have reported that metoclopramide (MCP), a dopaminergic antagonist, stimulates aldosterone secretion and that dopamine (DA) inhibits the MCP-mediated aldosterone secretion in man. However, many controversial results have been reported relating to the direct effect of MCP and DA on the secretion of aldosterone by adrenocortical cells in in vitro experiments. The present studies were designed to determine whether or not MCP and DA exerts its effect directly on the cultured human adrenocortical adenoma cells and adjacent non-adenoma cells obtained from patients with primary aldosteronism. A bolus intravenous injection of 10 mg MCP significantly increased the plasma aldosterone concentration (PAC) from 255 +/- 57 pg/ml (mean +/- SD) to 386 +/- 98 pg/ml after 15 min in patients with primary aldosteronism. But MCP (10(10)-10(-6) M) failed to increase aldosterone secretion from both adenoma cells and non-adenoma cells in culture. DA (10(-9) and 10(-6) M) did not suppress the basal secretion and the enhanced secretion of aldosterone by A II or ACTH in cells of either culture. The analysis by HPLC showed that 57% of dopamine hydrochloride added in the medium was preserved after 60 min incubation. These results suggest that MCP and DA do not act directly on the human adrenal glomerulosa cells in the regulation of aldosterone secretion.