: The toxicity of spinosad, a new insecticide derived from the bacterium Saccharopolyspora spinosa, was evaluated against susceptible and resistant strains of house Ñy (Musca domestica L.). Spinosad was highly toxic to house Ñies based on 72-h values and the symptoms of poisoning were consistent with LD 50 a neurotoxic mechanism of action. Spinosad was relatively slow acting, with the maximum toxicity noted at 72 h. Piperonyl butoxide and S,S,S,-tributylphosphorotrithioate synergized the toxicity of spinosad by 3É0-and 1É8-fold, respectively, while diethyl maleate had no signiÐcant e †ect. These results suggest that there is a small degree of monooxygenase-mediated spinosad detoxiÐcation in house Ñies, while hydrolases may be only minimally important and glutathione transferases may have no role. There were no substantial levels of crossresistance detected, except in the LPR strain where a low 4É3-fold cross-resistance was observed. The cyclodiene-resistant OCR strain was 2É7-fold more sensitive to spinosad than the susceptible strain (CS). These results suggest that cross-resistance may not be a limiting factor for the use of spinosad against house Ñies.1998 Society of Chemical Industry ( Pestic. Sci., 54, 131È133 (1998)