Synalbumin antagonist was investigated in a group of 48 siblings of diabetic children. Nine parents of these patients, 10 normal controls and 11 diabetic children were included in this study. In 26 of the 48 siblings synalbumin was detected. Glucose uptake by the rat hemidiaphragm was depressed from a mean of 13.36 to 0.99 mg% of glucose per 10 mg. of tissue in 90 min. incubation in the presence of 1,000 [mu]U. of insulin. In 5 of 9 parents tested, synalbumin was present. In only 3 of 14 families in which 2 or more siblings were studied was synalbumin absent. These findings suggest a familial distribution of the antagonist. Fasting blood sugar, glucose tolerance test and plasma insulin were normal in synalbumin positive siblings. Negligible amounts of immunoreactive insulin were detected in the albumin extracted from nondiabetic relatives. The synalbumin did not interfere with the immunoassay of insulin. In extracts of insulin-treated diabetics, various amounts of insulin were found. Five of 11 diabetics showed antagonism, 3 were border line, and 3 did not show antagonism. The results obtained suggest that synalbumin may be used as a genetic marker and encourage further investigation to assess the role of this inhibitor in the development of diabetes and as an indicator of prediabetes.