Pathophysiological implications of gender may be important in a number of disease states. We therefore decided to study the influence of gender on glycation in mice. Plasma glucose and glycated hemoglobin levels were determined by ion exchange (HbA1c) and/or affinity chromatography (GHb) in C57BL/6 ob/ob mice during the onset and subsequent decline of hyperglycemia. In preweanling ob/ob mice, glucose and glycated hemoglobin concentrations were equal to those of lean sex-matched controls. Shortly after weaning, plasma glucose in ob/ob mice increased to reach a maximum between 2 and 3 months of age, then declined over the next several weeks to levels within the range of lean mice. HbA1c values were closely associated with the glycemic changes. Male mice of both phenotypes consistently had higher values of glycated hemoglobin at a given glucose value than did females. Disappearance rates of chromium-labeled erythrocytes were slightly higher in lean female mice than in other subgroups but after correcting for phenotype/sex differences in blood volume, no phenotype or gender differences in RBC lifespan were observed. We conclude that there are gender differences in glycation of hemoglobin in mice and that factors other than RBC turnover are associated with the gender effects in both obese and lean mice.