Sodium valproate, a gamma-aminobutyric acid (GABA) agonist, was found to decrease plasma ACTH concentration in some cases of Cushing's disease and Nelson's syndrome. In this study we have investigated the influence of magnesium valproate (MV), a newly introduced salt of valproic acid, on plasma ACTH levels in 8 patients with Nelson's syndrome. The daily dose, 1200 mg of MV, significantly decreased plasma ACTH level at 10 p.m. compared with placebo. A single dose of 400 mg of MV, led to a reduction in plasma ACTH concentration only in two out of seven patients during a four-hour observation. The fall in plasma ACTH level in the same patients at 10 p.m., after the next two doses of this drug, suggests that single dose may be insufficient for introducing GABA-dependent reduction in ACTH release. During a long-term therapy with MV, in all three patients investigated a marked decrease in plasma ACTH was observed. Our results suggest that magnesium valproate may be useful during chronic therapy in some patients with ACTH hypersecretion.