We measured responses to pentobarbital of females and males of Sim:(LE) ancestry to test Long-Evans rats for a sex difference in drug response, i.e., higher pentobarbital susceptibility in females. We studied littermate quadruplets made up of an albino male and female and a black-hooded male and female to determine if the sex differences, if any, would be seen in both pigmented and albino rats. The rats were injected weekly IP with sodium pentobarbital; each rat's dosage increased 10 mg/kg per week to the dose that was lethal. In no case was the onset of the drug's effects consistently more rapid in the females. In both albino and hooded rats the drug effects' duration was significantly longer in the females. The females' lethal doses were lower than the males', but not significantly. Thus for at least one drug response measure there is a sex difference in drug response in pigmented and albino Long-Evans rats.