Myotonia can occur in the periodic paralyses, particularly the hyperkalemic form. The beneficial response to acetazolamide in hypokalemic and hyperkalemic periodic paralysis has led us to study the effect of acetazolamide in 9 patients with disorders having myotonia as the major problem, 7 with myotonia congenita and 2 with paramyotonia congenita. Patients were studied before acetazolamide administration with glucose and potassium loading tests. All patients had an increase in myotonia with potassium, but no weakness occurred with either test. Acetazolamide treatment decreased myotonia in all patients and in 3 proved the most satisfactory therapy. Side-effects during acetazolamide therapy included paresthesias in 5 patients and renal calculus in 1. Flaccid weakness occurred in a patient with paramyotonia congenita. Acetazolamide treatment was associated in all patients with partially compensated metabolic acidosis and lowering of serum potassium within the normal range. Kaliuresis was also noted during introduction of therapy. Acetazolamide appears to be an acceptable treatment for occasional patients with myotonia who are unresponsive to or intolerant of other therapies.