The varroa mite, Varroa destructor Anderson & Trueman, is a devastating pest of honey bees, Apis mellifera L., that has been primarily controlled over the last 15 yr with two in-hive miticides: the organophosphate coumaphos (Checkmite+), and the pyrethroid tau-fluvalinate (Apistan). Both coumaphos and tau-fluvalinate are lipophilic compounds that are absorbed by the wax component of the hive, where they are stable and have the potential to build up over repeated treatments such that bees could be exposed to both compounds simultaneously. Although these compounds were chosen as in-hive miticides due to their low toxicity to honey bees, that low toxicity depends, at least in part, on rapid detoxification mediated by cytochrome P450 monooxygenase enzymes (P450s). In this laboratory study, we observed a large increase in the toxicity of tau-fluvalinate to 3-d-old bees that had been treated previously with coumaphos, and a moderate increase in the toxicity of coumpahos in bees treated previously with tau-fluvalinate. The observed synergism may result from competition between miticides for access to detoxicative P450s. These results suggest that honey bee mortality may occur with the application of otherwise sublethal doses of miticide when tau-fluvalinate and coumaphos are simultaneously present in the hive.