One hundred and sixty patients with onset of non-ketotic diabetes at the ages of 35-70 were investigated for chlorpropamide-alcohol flush (CPAF), beta-cell function, insulin sensitivity, human leucocyte antigens (HLA), organ specific antibodies and diabetic complications. A positive flush reaction was defined as an increase in facial skin temperature by at least 1.5 degrees C, which was associated with a visible flush reaction in all patients. In accordance with these criteria, 38% of the patients were considered CPAF-positive with a mean rise in facial skin temperature of 2.3 +/- 0.1 degrees C compared with 0.6 +/- 0.1 degrees C in the CPAF-negative patients (p less than 0.001). The CPAF-positive patients could be distinguished from the CPAF-negative with respect to: 1) higher frequency of first degree family history of diabetes (p less than 0.05), 2) lower basal and glucagon-stimulated C-peptide concentrations (p less than 0.02 and p less than 0.001), 3) increased frequency of HLA-A2 (p less than 0.01) and decreased frequency of HLA-B7 (p less than 0.01). The findings thus support the genetically determined nature of CPAF. Considering the criteria for maturity onset diabetes in the young, it is unlikely that CPAF acts as a genetic marker for this particular form of genetic diabetes.