Selection of house flies (Musca domestica L.) with Isolate®(l-isopropyl-3-methyl-5-pyrazolyl dimethy1carbamate) resulted in a strain of flies with approximately 8-fold resistance to the insecticide. At the same time, aliphatic esterase activity in the selected strain declined to about 50% of that in the parent susceptible strain. The rate of decline in ali-esterase activity roughly paralleled the rate of increase in resistance. Genetic experiments indicated that resistance to Isolan and low aliphatic esterase activity were inherited in an identical manner and were either genetically linked or due to the same gene. Other experiments showed that flies of the resistant strain degraded Isolate at a higher rate than flies of the parent susceptible strain. The results suggest that the factor responsible for Iso-Ian resistance in the house fly strain studied is the same as the factor responsible for resistance to organophosphate insecticides in many fly strains. In both instances resistance is apparently due to mutant ali-esterases, which afford resistant strains an increased ability to degrade the insecticides to which they are resistant.