The authors investigated several features of polydrug use in rats. Heroin and cocaine were self-administered following responses on different levers, with only 1 drug and 1 lever available on alternate days of training. Four doses of each drug (heroin: 25, 50, 100, and 200 microg/kg/infusion; cocaine: 0.25, 0.5, 1, and 2 mg/kg/infusion) were tested, and each rat was exposed to a single dose combination. Rats readily developed drug-specific and dose-related responding. During extinction, rats displayed a significant bias for responding on the cocaine- associated lever. Priming injections of either cocaine (20 mg/kg) or heroin (0.25 mg/kg) reinstated responding that was selective for the lever previously associated with each drug. These results suggest that in this type of polydrug use, drugs have the capacity to activate drug-seeking behavior selectively oriented toward stimuli previously associated with their administration.