Because of the concern for potential neurotoxic effects (central nervous system excitation, convulsions) in the treatment of scabies using 1% lindane lotion, 5% permethrin cream has been suggested as an alternative scabicide. Using the finite dose technique, in vitro percutaneous absorption of 5% permethrin cream or 1% lindane lotion was measured in human and guinea pig skin following a single application. In vivo blood and brain levels of the scabicides were measured in guinea pigs following three daily applications of 5% permethrin cream or 1% lindane lotion. Permethrin and lindane levels were quantified by gas chromatography/mass spectroscopy. In vitro percutaneous absorption of the two scabicides was identical in guinea pig skin; however, human skin was 20-fold more permeable to lindane than to permethrin. In vivo guinea pig blood and brain levels of lindane were fourfold greater than permethrin levels. The risk for toxic effects, as assessed by systemic exposure during overuse conditions, is projected to be 40 to 400 times lower for 5% permethrin cream than for 1% lindane lotion.