The basal level of plasma immunoreactive glucagon-like peptide-1 (IR GLP-1) was significantly elevated in non-insulin-dependent diabetics (NIDD), and this elevation of IR GLP-1 was mainly due to an increase in the large component of IR GLP-1, corresponding to the pancreatic form. During the oral glucose-tolerance test (OGTT), the total plasma IR GLP-1 decreased in normal subjects but increased significantly in diabetic patients. Chromatographic analysis showed that IR GLP-1 consisted of several different molecular forms. OGTT caused a decrease in the pancreatic form but increased the intestinal form in normal subject, resulting into a net decrease in total plasma IR GLP-1. Whereas in NIDD the increase in the intestinal form was more prominent and the suppression of the pancreatic form was practically abolished to result in a net increase of total plasma IR GLP-1. This observation is consistent with the fact that in normal subjects the total change in IR GLP-1 was significantly correlated with both the total change of gut glucagon as well as that of pancreatic glucagon, but in diabetics the total change of GLP-1 only correlated to that of gut glucagon. The impaired suppression of pancreatic GLP-1 and enhanced release of intestinal GLP-1 could have some physiological importance in NIDD.