Studies were conducted in Wisconsin and Illinois, USA, to assess and compare the therapeutic and persistent efficacy of spinosad when applied as either a pour-on or topical spray and compared with cyfluthrin pour-on and coumaphos topical spray for controlling natural infestations of chewing (Bovicola bovis) and sucking (Linognathus vituli, Solenopotes capillatus and Haematopinus eurysternus) lice on cattle. Thirty-five animals at each trial site were blocked according to pre-treatment lice counts and randomly allocated to one of five treatment groups: single treatments of spinosad (25 g/L), diluted with water to 0.04% active ingredient and applied as a whole-body topical spray; spinosad (25 g/L) applied as a neat pour-on at 2 mg/kg body weight; Co-Ral Emulsifiable Livestock Insecticide (5.8% coumaphos), diluted to 0.03% active ingredient and applied as a whole-body topical spray; CyLence Pour-on Insecticide (1% cyfluthrin), applied as a neat pour-on at the manufacturer's recommended use rate for lice; and untreated control. Both spinosad treatments and cyfluthrin provided > or =96% control of B. bovis for up to 7 weeks, whereas the efficacy of coumaphos dropped to <90% after week 5 at one site. Spinosad spray had the best therapeutic and residual control of all treatments against L. vituli, > or =98% for at least 5 weeks at both sites, compared with 3 weeks for coumaphos at one site. Spinosad and coumaphos sprays provided 100% control of S. capillatus for at least 8 weeks compared with > or =97% control for spinosad and cyfluthrin pour-on treatments over the same interval. While H. eurysternus burden was low and limited to one study site, all four treatments provided 100% control for at least 6 weeks. These studies showed that topically applied spinosad provided a high degree of therapeutic and residual control against both sucking and chewing lice.