Eleven patients with Nelson's syndrome were given sodium valproate (Epilim, Sanofi). Plasma ACTH and cortisol levels were measured under carefully controlled conditions which were designed to eliminate spontaneous fluctuations in ACTH. At 6 weeks all 11 patients were reassessed while taking sodium valproate 600 mg/day; there was then a small but significant (P less than 0.05) reduction in plasma ACTH concentration. Six patients continued to take sodium valproate, and were reassessed at 1 year when five were taking 1200 mg/day and one patient was taking 600 mg/day. At 1 year for these six patients there had been an increase in mean plasma ACTH which was then not significantly different from basal values. The five patients who discontinued sodium valproate were also reassessed at 1 year, when there were no significant differences compared to basal or 6-week values. During therapy with sodium valproate, there were no significant changes in the half-life of plasma cortisol, plasma sodium and potassium concentrations, or serum liver enzymes. Weight gain on sodium valproate was the main reason for patients asking to discontinue therapy. Sodium valproate is not an effective long-term therapy for reducing plasma ACTH for patients with Nelson's syndrome.