To evaluate the effect of levamisole therapy combined with corticosteroid in children with nephrotic syndrome and frequent relapses (FR) or steroid dependence (SD), we studied retrospectively 24 children (18 boys and six girls) with a mean age of 32 months. Eleven (46%) patients had FR and 13 (54%) had SD. Levamisole was used for a mean period of 8.5 months. The relapse rate decreased from a mean of 4 relapses/year during steroid therapy alone to 1.3 relapses/ year during the combined therapy in 17 (71%) of the patients. Remission was sustained, after discontinuing levamisole, for more than six months in 11 of the 17 responders (65%), and six patients relapsed after discontinuing levamisole. Seven of the 24 study patients (29%) had no response to levamisole. The seven patients who failed to respond to levamisole and the six initial responders who could not maintain remission after discontinuing the drug were treated with cyclophosphamide for 12 weeks. Eight of these patients (61.5%) had remission sustained for a mean duration of 10 months. The FR patients sustained remission for a longer period of time than SD patients in both groups. Levamisole was more effective than cyclophosphamide in patients with the age of onset of the disease above 2 years (10 patients out of 11 (91%). The side effects of levamisole and cyclophosphamide in our patients were transient and manageable. We conclude that levamisole is a safe and effective drug if combined with corticosteroid therapy in children with nephrotic syndrome. Further studies may be required.