The Mazzotti reaction is a frequent complication in patients with onchocerciasis being treated with diethylcarbamazine (DEC); and more severe manifestations of this reaction may be unacceptable in many patients. It has recently been demonstrated that prednisone modifies the severity of this reaction and reduces the microfilaricidal activity of DEC. A clinical trial was performed at the National Leprosy Training Center in Wau, Sudan, to evaluate the clinical and histologic effect of the use of corticosteroids in patients receiving DEC. Administration of a low dose of dexamethasone (3 mg/day), begun after onset of the Mazzotti reaction, modifies the progression of the Mazzotti reaction without interfering with the microfilaricidal efficacy of DEC. Pretreatment with low-dose dexamethasone--prior to beginning DEC therapy--prevents the development of the Mazzotti reaction and greatly reduces the microfilaricidal activity. Administration of diphenhydramine, after onset of the Mazzotti reaction, has no effect on the course and intensity of the Mazzotti reaction nor on microfilaricidal activity. We recommend that low-dose corticosteroids be administered in conjunction with DEC--after onset of the Mazzotti reaction--and that they be tapered rapidly.