Twelve inhibitors of eicosanoid biosynthesis were examined for their ability to affect the response of insect cells in vitro and developing larvae to delta-endotoxin from Bacillus thuringiensis. The response of cultured insect cells from Manduca sexta, Choristoneura fumiferana, and Plodia interpunctella to CryIA(c) and CryIC protein from Bacillus thuringiensis was measured while exposed to various concentrations of specific cyclooxygenase and/or lipoxygenase inhibitors. Five of the inhibitors (curcumin, baicalein, nordihydroguaiaretic acid, indomethacin, and eicosatetraynoic acid) were toxic to the cells at high concentrations (> 20 mu M). Surprisingly, the same inhibitors had no significant effect upon normal larval development, except for nordihydroguaiaretic acid. No true, consistent difference was detected with either lipoxygenase or cyclooxygenase inhibitors for cells or larvae treated with delta-endotoxin. However, the delta-endotoxin response of insect cells in vitro and developing larvae in the presence of nordihydroguaiaretic acid was strong evidence of an involvement with P-450 cytochromes in the B. thuringiensis toxic response.