The binding of [3H][D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [3H][D-Pen2,5]enkephalin (DPDPE), [3H]ethylketocyclazocine (EKC), and [3H][Met5]enkephalin (MET) was used to examine mu-, delta-, kappa-, and zeta-receptors, respectively, in the developing (birth to postnatal day 19) and adult human cerebellum. Specific and saturable binding of all ligands was recorded in developing brains, and of [3H]DAGO, [3H]DPDPE, and [3H]EKC in adult cerebellum; all data fit a single homogeneous binding site for each ligand. However, the ontogenic profile of opioid receptor subtypes differed. Delta- and kappa-receptor capacities were 7.8- and 3.6-fold, respectively, greater in infant cerebellum than in adults. The mu-receptor decreased over 7-fold in both binding affinity and capacity after day 2; by adulthood, the binding affinity was the same as in newborns but only one-half the binding capacity was recorded. The concentration of zeta-receptors was 20-fold greater in subjects 2-19 days of age than in newborns. These data demonstrate the presence, and distinct developmental profiles, of opioid receptors in human cerebellum. Although the function of mu-, delta-, and kappa-receptors in human cerebellum are unclear, the growth-related zeta-receptor is present at a time of cell replication and differentiation but is not detected in mature cerebellum.