The prevalence of low insulin responders was assessed in non‐diabetic subjects with various patterns of family history of diabetes. Subjects were divided into five groups: group A, without any family history of diabetes among all known relatives; group B, with diabetes among parents and/or siblings; group C, with one diabetic parent; group D, with two diabetic parents; and group E, non‐diabetic co‐twins of monozygotic twins with diabetes. Except twins, the type of diabetes in the family was not defined. They were examined by 1 00 g oral glucose tolerance test (OGTI) except for group E in which 50 g or 75 g OGTI were also used. Insulin response was evaluated by the insulinogenic index, the ratio of increment of serum insulin to that of plasma glucose (mg dl⁻¹) 30 min after the oral glucose load. The low insulin responders had a lower insulinogenic index below 0.5 in the case of 100 g OGTI, and below 0.35 and 0.4 in the case of 50 g and 75 g OGTI. Groups with a family history of diabetes (B, C, and D) had significantly lower insulinogenic indices than group A without a family history of diabetes. The prevalence of low insulin responders was significantly higher in subjects with a strong family history of non‐insulin‐dependent diabetes mellitus (NIDDM), such as subjects with two diabetic parents and monozygotic co‐twins of NIDDM patients. In group A, low insulin responders were more prevalent in older subjects, while in group D, they were also frequent in younger subjects. These results suggest that a low insulin response has a genetic basis and is a preclinical feature in subjects with genetic pre‐disposition to NIDDM.