Neurocysticercosis, occasionally associated with long-term neurologic sequelae such as epilepsy or hydrocephalus, is more often a condition characterized by a benign course and spontaneous remission without permanent neurologic symptoms. This variability in outcome has led to difficulties in the interpretation of studies of the effectiveness of drugs used to treat this condition. To evaluate the relative efficacy of two antihelminthic agents against each other and against symptomatic treatment alone. Randomized clinical trial of treatment of patients with newly identified active neurocysticercosis with oral prednisolone alone (27 patients), praziquantel with prednisolone (54 patients), or albendazole with prednisolone (57 patients). At 6 months and at 1 year after treatment, there were no differences in the three treatment groups in terms of the proportion of patients who were free of cysts or the relative reduction of number of cysts. At 2 years, there was no difference in the proportion of patients free of seizures during the entire follow-up period. Early and late sequelae occurred in a higher proportion of patients treated with praziquantel and albendazole, compared with those receiving only prednisolone. Previous reports of favorable response to treatment of neurocysticercosis with either praziquantel or albendazole are by no means definitive and may be a reflection of the natural history of the condition. The present study, with randomized treatment assignment and including a control group, raises questions as to what extent and in whom treatment with these drugs is effective, and suggests that treatment with antihelminthic agents may be associated with an increased frequency of long-term sequelae.