alpha-Melanocyte-stimulating hormone (alpha-MSH) modulates inflammatory processes in models of acute inflammation and in models of sepsis/septic shock/adult respiratory-distress syndrome (ARDS). Because this neuropeptide inhibits actions of cytokines and other mediators of imflammation that are also believed to underlie aspects of chronic inflammation, tests were performed to compare the effects of repeated administration of the peptide with those of prednisolone and saline on the development of adjuvant arthritis in rats. alpha-MSH (50 micrograms), injected i.p. twice daily, markedly inhibited the clinical and histological signs of experimental arthritis and moderated the weight loss observed in control animals. Prednisolone (100 mg/kg), given twice per day, prevented development of arthritis but caused marked and progressive weight loss. The results confirm the potent anti-inflammatory influence of alpha-MSH, in this case in a model of chronic inflammation that has immune components.