The nature of circulating pro-opiomelanocortin (POMC)-related peptides was investigated in patients with a diagnosis of septic shock. Also, changes following administration of methylprednisolone were monitored using established chromatographic techniques and three radioimmunoassays directed towards the N-terminal, mid-portion and C-terminal regions of the precursor. Adrenocorticotrophin and beta-endorphin-like peptides were identified in the circulation. By 60 min after a pharmacological dose of methylprednisolone (30 mg/kg) concentrations of these peptides were reduced and continued to fall up to 180 min. beta-Lipotrophin and N-terminal POMC(1-76) were also detected by the beta-endorphin and gamma 3-MSH assays respectively. The concentrations of these peptides were noticeably reduced only after 180 min. The 31,000 Da MSH/ACTH/beta-endorphin (POMC) and the 22,000 Da MSH/ACTH precursors were also present in the circulation in septic shock and their concentrations increased following steroid treatment.