BACKGROUND: Resistance to the pyrethroid insecticide deltamethrin has been a growing problem in the management of Helicoverpa armigera (Hübner) pest populations in West Africa. Detoxification by P450 enzymes appears to be a major mechanism of resistance, but the genes responsible for resistance are unknown. RESULTS: First, it was shown that deltamethrin resistance in strains from Burkina Faso (Kaya) and from Spain (Seville) were suppressible by piperonyl butoxide and by trichlorophenyl propynyl ether, thus indicating a major role of P450 enzyme(s) in resistance. The larval expression of 21 CYP genes encoding P450 enzymes from six CYP families were then compared by quantitative RT-PCR. Five genes, CYP4L5, CYP4L11, CYP6AE11, CYP332A1 and CYP9A14, were significantly overexpressed in the Kaya and Seville strains when compared with Heliar, a susceptible strain. Significant overexpression of multiple CYP genes (CYP4M6, CYP4M7, CYP6AE11, CYP9A12, CYP332A1 and CYP337B1) was also found in six field strains with different levels of resistance from Benin, Burkina Faso andMali. CONCLUSION: Although functional or genetic evidence for the role of these P450s in resistance remains to be formally established, results suggest that multiple P450 enzymes contribute to deltamethrin resistance. This study is a first step towards the development of molecular tools for the detection of P450-based resistance in H. armigera.