It has been found that the effects of opiates and opioid peptides on RVD are of two types. Compounds of the first type such as Etor, Eton, fentanyl and prodine derivatives, Met- and Leu-Enk and DADL are biphasic in nature. At lower concentrations (10(-8)-10(-5) M) they have inhibitory effects and at higher concentrations (10(-5)-10(-4) M) they are excitatory. Compounds of the second type, such as Mor, benzomorphan derivates, Cyc and SKF and the antagonist Nx have virtually no or only weakly inhibitory effects but may antagonize the inhibitory effect produced by the first group of compounds at lower concentrations. MC belongs to the second type, but it cannot antagonize the inhibitory effect of beta-End. The results are discussed in terms of multiple receptors, the high and low affinity binding sites, and the interrelationship between receptors.