Background: The conventional antiscabietics have poor compliance. Ivermectin, an oral antiparasitic drug, has been shown to be an effective scabicide and could be a useful substitute. Objective: This study compares the efficacy of oral ivermectin with topical permethrin cream in the treatment of scabies. Methods: Eighty-five consecutive patients were randomized into 2 groups. Forty patients and their family contacts received 200 μg/kg body weight of ivermectin, and another 45 patients and their family contacts received a single overnight topical application of 5% permethrin cream. Patients were followed up at intervals of 1, 2, 4, and 8 weeks. Results: A single dose of ivermectin provided a cure rate of 70%, which increased to 95% with 2 doses at a 2-week interval. A single application of permethrin was effective in 97.8% of patients. One (2.2%) patient responded to 2 applications at a 2-week interval. Permethrin-treated patients recovered earlier. Conclusion: A single application of permethrin is superior to a single dose of ivermectin. Two doses of ivermectin is as effective as a single application of permethrin. The temporal dissociation in clinical response suggests that ivermectin may not be effective against all the stages in the life cycle of the parasite. (J Am Acad Dermatol 2000;42:236-40.)