The therapeutic efficacy and tolerance of a single application of 1% permethrin cream rinse, applied for ten minutes, and a single application of 1% lindane shampoo applied, as recommended by the manufacturer, for four minutes, against the head louse Pediculus humanus var capitis were compared in a single-blinded, randomized, controlled clinical trial. Of 573 patients enrolled at eight centers, 559 were assessable for tolerance and 508 for efficacy. Of the 257 patients treated with 1% permethrin cream rinse, 99% were lice free at 14 days; of the 251 patients treated with 1% lindane shampoo, 85% were lice free at 14 days. The difference is statistically significant. For both treatments, adverse experiences were infrequent, mild, and usually difficult to distinguish from the symptoms of head lice infestation. A single ten-minute application of 1% permethrin cream rinse was well tolerated, highly effective, and therapeutically superior to a single four-minute application of 1% lindane shampoo.