Rats of the Lewis inbred strain have been shown to self-administer more morphine than rats of the inbred Fischer 344 (F344) strain. Because morphine reward and opioid-induced feeding may involve a common mechanism, we measured whether these strains also differ in their feeding response to morphine. In Experiment 1, rats were maintained on powdered rat chow and given SC injections of morphine sulfate (1, 3, and 10 mg/kg) and saline; all rats were tested with all doses. Food intake was measured 2, 4, and 6 h after injection. In Experiment 2, rats were given a choice of two diets: a fat/protein diet and a carbohydrate/protein diet. Feeding responses to morphine were measured in a manner identical to that in Experiment 1. In both experiments, the feeding response to morphine was greater in Lewis rats than in F344 rats. To determine whether these responses might be explained by differences in the levels of morphine achieved in the blood or brain, rats of each strain were given SC injections of morphine sulfate (3 mg/kg) and sacrificed either 30 min or 3 h after injection. Serum and brain morphine levels were determined by radioimmunoassay. Lewis rats had significantly less brain morphine than F344 rats at 30 min; they did not differ in morphine content at 3 h. Serum levels were similar at 30 min; at 3 h, F344 rats had slightly lower levels than Lewis rats. Thus, differences in tissue levels cannot readily explain the differences in feeding responses to morphine.(ABSTRACT TRUNCATED AT 250 WORDS)