The insecticidal activity of spinosad was evaluated against susceptible and permethrin-resistant human lice. In a permethrin-susceptible strain of the body louse, Pediculus humanus humanus L. (Anoplura: Pediculidae), the toxicity of spinosad was similar to that established for permethrin, with an LD₅₀ value of 1.2 ng/insect and 2.4 ng/insect, respectively. Topical application of spinosad to populations of permethrin-resistant head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), showed that susceptibility to spinosad was independent of resistance to permethrin. The effectiveness of spinosad against human lice and the low mammalian toxicity reported in the literature suggest that spinosad could be useful for the management of permethrin-resistant human lice.