Degradation of a regulatory peptide ACTH(4-10) and its synthetic analog semax in rat blood and serum was studied using high-performance liquid chromatography. About one third to one half of the serum degrading activity could be ascribed to bestatin-sensitive aminopeptidase which cleaved first and second N-terminal residues Met and Glu producing relatively stable intermediates. Comparable areas under the degradation/accumulation curves for intact peptides and intermediates implied that the latter can contribute to effects of intact peptides. Semax turned out to be more stable than ACTH(4-10) against the action of other enzymes that took part in degradation.