Gastric inhibitory polypeptide (GIP), a hormone secreted from the proximal small gut, is recognized as a major component of the enteroinsular axis. However, circulating levels of GIP in diabetes have been reported to be exaggerated, normal or decreased following glucose ingestion, which may be due to the presence of variable crossreacting immunoreactive GIP forms in the circulation. We have raised an antibody (S705) which recognizes only 5 kDa GIP. Using this antiserum we have measured circulating GIP levels in 18 healthy volunteers, and 13 Type 2 diabetic and 9 Type 1 diabetic patients following ingestion of 75 g glucose. As expected, blood glucose levels and blood insulin levels are significantly abnormal in the diabetic groups. On the other hand, circulating GIP levels at all time-points and integrated incremental GIP over 120 min were not different from the control group. However, we cannot exclude the possibility that apparently normal immunoreactive GIP levels in diabetes might conceal subtle alterations in biological activity which could play a role in the pathogenesis of the disease.