Twelve patients with retinitis pigmentosa and chronic macular edema were prospectively treated for 2-week periods with acetazolamide or a placebo in a masked, crossover study. Ten of the 12 patients had both subjective and objective improvement in visual acuity when treated with acetazolamide. Improvement was seen even in patients with an acuity as good as 20/25 at baseline as well as in patients with macular edema present for more than a decade. A dosage of 500 mg/d was found to be more effective than 250 mg/d. Six patients (50%) showed lessening of their macular edema on fluorescein angiography. This angiographically demonstrated improvement was predominantly due to less detectable leakage from retinal capillaries rather than from choroidal capillaries through the retinal pigment epithelium. Improvement in visual acuity was seen in some patients without a detectable change in the amount of angiographic fluorescein leakage.