The response to plasma immunoreactive gastric inhibitory polypeptide (GIP) to oral glucose loading was determined in 10 normal subjects, 10 patients with mild diabetes mellitus, and 10 patients with moderate to severe diabetes mellitus. In normal subjects the mean fasting GIP was 167 +/- 17 pg/ml which rose significantly after glucose loading, reaching the peak value of 513 +/- 44 pg/ml at 30 min. In mild diabetic patients, fasting plasma GIP was not significantly different from that in normal subjects. However, the mean peak GIP level following glucose loading was 683 +/- 71 pg/ml, significantly higher than that in normal subjects (p less than 0.05). In moderate and severe diabetics, oral glucose loading caused an abrupt rise in plasma GIP from the basal level of 304 +/- 31 pg/ml to the peak of 870 +/- 63 pg/ml occurring at 30 min, both of which were significantly higher than the corresponding values in normal subjects (p less than 0.01). These results suggest that GIP response to oral glucose loading is enhanced in diabetic patients in proportion to the degree of their glucose intolerance.