Some hemodialysis patients, without taking any acnegenic agents, developed severe nodulocystic acne with unknown causes. Because nodulocystic acne poorly responds to conventional acne therapy and increases the black pigmentation in the face, it severely interferes with the quality of life of these patients. To investigate whether isotretinoin is effective in treating hemodialysis patients with severe nodulocystic acne, we undertook a prospective, randomized, single-blind study. A total of 20 patients with nodulocystic acne participated in the study, of whom 18 completed it. Ten patients received isotretinoin 10 mg/day (5 mg/capsule) for 3 months as a study group and the other 10 took placebo for 3 months as a control group. The severity of acne and treatment-related side effects were evaluated monthly by a questionnaire and laboratory evaluation which included liver function tests, blood lipids and blood platelet counts. The results showed isotretinoin treatment significantly reduced the severity of acne of the study group patients after 1 month (scales of acne severity: 4.0 +/- 0.0 vs. 3.13 +/- 0.35, p < 0. 01) and 3 months (4.0 +/- 0.0 vs. 1.5 +/- 0.76, p < 0.01) of follow-up. In addition, the severity of acne of the study group patients was significantly less than that of the control group patients after 1 month (3.13 +/- 0.35 vs. 3.80 +/- 0.42, p < 0.01) and 3 months (1.5 +/- 0.76 vs. 3.70 +/- 0.48, p < 0.001) of treatment. Only mild side effects were noted. No significant changes of biochemical evaluation were found except that a mild elevation of aspartate aminotransferase was noted in the study group patients. However, two study group patients withdrew from the trial because of isotretinoin-related side effects and toxic hepatitis. In summary, our study first demonstrated that the small dose of isotretinoin effectively treated nodulocystic acne of hemodialysis patients and the side effects were mild. This result suggests that isotretinoin may be the treatment of choice for nodulocystic acne in end-stage renal disease patients with renal replacement therapy. The liver function and other isotretinoin-related side effects in these patients should be carefully monitored.