Receptor-selective opioid agonists have been found to suppress the capacity of macrophages to ingest opsonized sheep erythrocytes. In an effort to characterize the immunomodulatory activity of opioids further, experiments were done to examine the uptake of Candida albicans by opioid-treated murine peritoneal macrophages. It was found that treatment with morphine and selective mu, i.e., DAMGO, delta, i.e., DPDPE, and kappa, i.e., trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzene-acetamide methanesulfonate, receptor agonists resulted a concentration-dependent suppression of both the percentage of phagocytic cells and the average number of ingested yeasts. Antagonists selective for mu, i.e., H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, delta, i.e., naltrindole, and kappa, i.e., norbinaltorphimine, opioid receptors completely blocked the respective receptor-selective agonist-induced suppression. These results suggest that the mu, delta and kappa opioid receptors can modulate macrophage function.