Pancreatic beta cell function in response to glucose was assessed in three different groups of offspring of conjugal diabetic parents (OCDP): those with normal glucose tolerance, those with impaired glucose tolerance (IGT), and those with diabetes. Serum immunoreactive insulin (IRI), C-peptide (CP), insulin/glucose (I/G) ratio, and IRI/CP ratios were estimated at fasting and 90 min after glucose load. Insulin secretion, measured as CP, was found to be low even in normal nonobese OCDP, but the change was not reflected in IRI value as the IRI/CP ratio was found to be elevated. The values decreased with increasing glucose intolerance. In obese OCDP, all the parameters were abnormal even among those with normal glucose tolerance, and further deterioration occurred with increasing glucose intolerance. The study shows that insulin secretory defects are detectable even in normal OCDP, and these changes deteriorate with increasing glucose intolerance. Differences are noted in the peripheral concentrations of IRI and CP between obese and nonobese OCDP before development of diabetes. After development of diabetes mellitus, these differences disappear, and the CP and IRI values in both groups are similar and low.