For the metabolic characterization of immunocompetent cells which are involved in the development of an insulin-dependent diabetes, a method for measurement of adenine uptake by mononuclear and macrophage-depleted mononuclear cell populations and of incorporation rates into the ATP, ADP, AMP and hypoxanthine fractions of these cells is presented and examined for its informative value in a cross-sectional study of individuals at risk of developing insulin-dependent diabetes. Values of 30 controls were compared with those of 53 risk persons. In controls and in 28 of the risk persons the adenine uptake by mononuclear cells was two to three times higher than that by the macrophage-depleted mononuclear cell population, suggesting high adenine metabolic activity of phagocytic cells. This activity was significantly decreased in the phagocytic cells of the remaining 25 risk persons. Additionally, the adenine incorporation rates into the adenine nucleotides of mononuclear cells were reduced by approximately 50% in these 25 risk persons. The alterations of purine metabolism were found associated with clinical symptoms of transient alterations of glucose tolerance and in the case of manifestation with a mild (HLA DR 3) type of insulin-dependent diabetes.