A multicenter, randomized, investigator-blind controlled trial was conducted to compare the safety and efficacy of a single, whole-body application of 5% permethrin cream with that of 1% lindane lotion for the treatment of scabies in 467 patients. At 14 +/- 3 days after treatment, the mean active lesion count decreased from pretreatment levels of 85 (range, 4 to 600) in both treatment groups to 14 (range, 0 to 133) in the permethrin group and to 15 lesions (range, 0 to 500) in the lindane group. At 28 +/- 7 days after treatment, complete resolution had occurred in 181 (91%) of 199 patients treated with permethrin and in 176 (86%) of 205 patients given lindane. Pruritus due to scabies persisted at 28 +/- 7 days in 14% of the permethrin group and in 25% of the lindane group. The most frequent adverse effects were new or increased pruritus and mild, transient burning or stinging; the latter was slightly more frequent following permethrin treatment and appeared to be related to severity of infestation. Because of a lower potential for neurologic toxicity, permethrin may be preferable to lindane for the treatment of scabies particularly in children.