1. The influence of diets differing in protein concentration on the characteristics of mu, delta, and kappa-opiate receptors and on the analgesic and hyperthermic responses to morphine was examined in rats. Three groups of male Sprague-Dawley rats were maintained for four weeks on isocaloric diet containing either 4, 20 or 50% protein. 2. The animals maintained on 4% protein diet weighed 92 +/- 2% of the initial weight at the end of the fourth week, whereas animals maintained on 20% and 50% protein diet weighed 222 +/- 2% and 221 +/- 2%, respectively. The average food intake per 100 g body weight on day 1 of the study in 4, 20 and 50% protein diet group was 5.0 +/- 2.2 g, 10.4 +/- 1.4 g, and 10.0 +/- 1.2 g, respectively. This difference in food intake was not observed during rest of the period of the study. 3. Water intake was higher for the animals maintained on diet containing 50% protein as compared to the other two groups. 4. The analgesic and the hyperthermic response to morphine varied in direct relation to the concentration of protein in the diet. The concentration of morphine in the brain and plasma of animals maintained on the three diets following challenge dose of morphine did not differ. Similarly the Bmax and Kd values for the binding of [3H]naltrexone, [3H]D-Ser2-Thr6-leucine enkephalin and [3H]ethylketocyclazocine to brain membranes prepared from rats kept on 4, 20 and 50% protein concentration did not differ. 5. It is concluded that the diet differing in protein concentration can alter the responses to morphine, and that such altered effects can not be accounted for by the changes in the distribution of morphine in brain and plasma or to the changes in the characteristics of the mu, delta and kappa opiate receptors in the brain.