Dopamine is likely an important physiological melanotropin release-inhibiting factor in amphibians. This study concerns the effects of dopamine on the biosynthesis and release of peptides from the pars intermedia of the frog Rana ridibunda. Our results show that this secretagogue has no immediate effects on either the rate of biosynthesis of pro-opiomelanocortin nor on the direction of processing of this prohormone. Pulse-chase experiments revealed that dopamine inhibited the release of all newly synthesized POMC-related peptides in a dose-dependent manner. For each dopamine concentration tested, the degree of inhibition exerted on the release of the various newly synthesized peptides by a given concentration of secretagogue was approximately the same, with the exception of that found for the alpha-MSH related peptides. Analysis of the release of these melanotropins was complex because dopamine not only inhibited their release but also, either directly or indirectly, inhibited the acetylation reaction which converts des-N alpha-acetyl alpha-MSH to alpha-MSH. Dopamine was shown to be less potent in inhibiting the release of des-N alpha-acetyl alpha-MSH than inhibiting release of the acetylated form of the peptide. In amphibians a preferential release of the less-bioactive non-acetylated form of MSH under inhibitory conditions induced by dopamine may be of physiological importance.