Degenerative kidney changes are associated with heroin use in human addicts, but it is not known whether these changes result from exposure to the opioid or from contaminants in street heroin. In the present study, 4-6-month-old rats each received 1 subcutaneous pellet containing 75 mg of morphine or placebo, followed 3 days later by implantation of 2 additional morphine or placebo pellets. Seven days after implantation of the first pellet, the rats were killed by aldehyde perfusion. The right kidney was excised, and coronal slices were prepared for scanning electron microscopy. Micrographs were taken at 5000X and were scored on the presence of short or long microprojections (a score of '1' indicating few and a score of '4' indicating many). Morphine significantly altered the frequencies of scores for long microprojections, suggesting that morphine treatment increased the number of microprojections on glomerular podocytes. No changes in filtration slits, pedicels, or blebbing (foval enlargements) were noted. The data support the view that kidney degeneration associated with opioid abuse reflects effects of opioids per se, and they are consistent with microprojection changes as a function of altered intracellular cyclic AMP levels.