We have previously demonstrated that [3H]dynorphin A selectively labels kappa opioid receptors in guinea-pig whole brain. In these current studies, using protection from inactivation by beta-chloronaltrexamine (beta-CNA), we are able to demonstrate that although dynorphin A prefers kappa receptors, it will label mu receptors when kappa receptors are not available, or present in only a small number. Thus, differences in numbers of mu and kappa receptors present in brain preparations are critical in determining the receptor binding profile of [3H]dynorphin A across species. Additionally, although all the prodynorphin derived peptides show kappa preference, the ability of the other prodynorphin derived peptides to compete with [3H]dynorphin A for its receptor varies across species. Consequently, in a highly enriched kappa preparation such as monkey cerebral cortex, [3H]dynorphin A appears to label kappa receptors with substantial selectivity, and the other prodynorphin-derived peptides show less ability to compete with dynorphin A for its receptor. In contrast, in a kappa-poor tissue such as rat brain, all of the prodynorphin-derived peptides, including dynorphin A-(1-8), show very similar potency. Thus, differences in mu and kappa receptor numbers across brain regions and species lead to differences in the receptor binding profile of dynorphin A.