A radioimmunoassay for immunoreactive gamma-MSH (IR-gamma-MSH) in human plasma has been developed. The assay is capable of detecting normal basal circulating levels which range from less than 20-100 ng/1 at 0900 h. Plasma levels are raised concomitantly with ACTH during insulin induced hypoglycaemia and CRF stimulation and suppressed with dexamethasone. Chromatographic characterisation of IR-gamma-MSH in plasma demonstrates a major peak of IR-gamma-MSH, corresponding to purified glycosylated N-terminal pro-opiomelanocortin 1-76, when IR-gamma-MSH is secreted from the pituitary. In contrast IR-gamma-MSH produced ectopically appears to be heterogeneous.