The phenotypic expression of the three opioid receptors kappa, mu and delta was determined in the rat and guinea pig cerebellum during ontogeny. In both species, the increase in cerebellum weight was accompanied with a gradual increase in the total number of opioid receptors. At the same time, however, the receptor concentration (femtomoles per milligram protein) fluctuated, and finally declined by 3.3- and 2.0-fold in the adult rat and guinea pig cerebella, respectively. In the guinea pig, kappa receptors constituted about 80% of the receptors at the earliest developmental stage tested, day 20 of the embryo, but then there was a sharp decrease in this value, resulting from an increase in both mu and delta receptors. This decrease was, however, transient, and the percentage of the kappa receptors increased again to reach 77% of the receptors in the adult cerebella. A similar transient increase in the percentage of mu and delta receptors was observed during the development of the rat cerebellum, although the receptor density in this species was 1/4-1/8 that of the guinea pig. Cultures of aggregating guinea pig cerebellar cells were used to further study the factors regulating the expression of the three opioid receptors in this brain region. The possibility that the development in vivo of cells expressing different opioid receptors is associated with the ontogeny of the endogenous opioid peptides is discussed.