Although acetazolamide usually prevents paralytic attacks in hypokalemic periodic paralysis, not all patients benefit from this treatment. We studied a father and two sons in whom attack frequency and severity increased on acetazolamide. Administration of triamterene virtually abolished attacks in three separate single-blind trials totaling more than 12 months. Spontaneous and glucose-insulin provoked attacks occurred with only slight hypokalemia. Acetazolamide produced slight hypokalemia and provoked attacks of weakness whereas triamterene increased potassium levels significantly. Certain patients with hypokalemic periodic paralysis are worsened by acetazolamide, perhaps because of its kaliopenic effect. Triamterene may be effective in some of these patients.