Using a highly specific radioimmunoassay we have measured the concentrations of human growth hormone releasing factor (ir-hGRF) in the peripheral circulation of six individuals with acquired hypothalamic hGRF deficiency. Despite their hypothalamic dysfunction venous plasma ir-hGRF increased normally in every patient after the stimulus of a mixed breakfast, from an average concentration basally of 13.6 +/- 6.0 pg/ml to a maximum of 29.0 +/- 8.4 pg/ml (mean +/- SEM) at 120 min. The findings indicate that circulating hGRF is at least in large part extrahypothalamic in origin, which in turn implies a physiological role for hGRF in the periphery.