Consumption of the drug phenobarbital is known to influence cytochrome P450 monooxygenase (P450) activity in so many organisms that it has come to be known as a “universal P450 inducer”. Recent microarray analysis of Drosophila melanogaster treated with phenobarbital showed induction of nearly one-third of the fly's P450 inventory as well as repression of a small number of P450s. Induction of P450s can increase rates of metabolism of xenobiotics, rendering phenobarbital-treated insects more tolerant of insecticides. The honey bee genome encodes 46 P450s, most of which, aside from those involved in ecdysteroid metabolism, cannot be assigned a potential function. Bees given candy laced with phenobarbital show a marked and unexpected decrease in tolerance of the pyrethroid pesticide tau-fluvalinate, which is detoxified by P450s, suggesting possible repression of the P450 responsible for breaking down tau-fluvalinate in untreated bees. Aldrin, an organochlorine insecticide which is bioactivated by P450s, also becomes more toxic to bees treated with phenobarbital, suggesting that the bioactivating P450 is induced by phenobarbital treatment. Comparing the P450 gene expression between phenobarbital treated and untreated bees may shed light on which P450s are responsible for tau-fluvalinate detoxification and aldrin bioactiviation.