Using a synthetic C- terminal tetradecapeptide of human islet amyloid polypeptide (IAPP), we prepared an antiserum for human IAPP [24-37] and established a highly sensitive radioimmunoassay (RIA) for human IAPP. Analyses of human pancreatic extract using reverse-phase high performance liquid chromatography coupled with the RIA revealed that the antiserum specifically detects human IAPP. The content of IAPP in the pancreas of two non-diabetic patients was 604.0 and 1447.7 pg/mg wet weight, and a small amount of IAPP-immunoreactivity was detected in the stomach, duodenum, and jejunum. The mean plasma concentration of IAPP in 10 normal individuals was 13.5 +/- 4.8 (SD) pg/ml. The RIA established in this study provides a useful tool to elucidate the physiological function of IAPP and its pathophysiological significance in non-insulin-dependent diabetes mellitus (NIDDM).