The effects of chronic administration of morphine (20 mg/kg) on self-stimulation (SS) of the central gray and lateral hypothalamus were investigated in a within-subject design. The magnitude and time course of the drug-produced changes in SS at the two placements were similar within subjects but varied substantially across subjects. These results are interpreted in the light of evidence pertaining to the anatomical linkage of the substrates for the rewarding effects of central gray and lateral hypothalamic stimulation. The facilitation of SS may be due to a drug-produced sensitization of reward-related neurons. If so, morphine acts either beyond the point of convergence of the two substrates or at an earlier stage in each substrate. The across-subject variability is attributed to individual differences in sensitivity to the effects of the drug. The importance of controlling for this subject variable is stressed.