We previously have shown that an affinity, high-performance liquid chromatography (HPLC) method is a highly reproducible and sensitive method for determining percent total glycohemoglobin (tGHb) in people with diabetes. In this study we extended the use of this method to a determination of the correlation of percent tGHb with the fasting plasma glucose concentration in people without known diabetes. We also determined the correlation of the tGHb with the reticulocyte count, as an index of red blood cell (RBC) survival, and with a carbon monoxide (CO) method for determining RBC survival. In addition, the stability of the tGHb, glucose, RBC mass, hemoglobin, and reticulocyte counts over a 1-year period was evaluated. Total glycohemoglobin, overnight fasting plasma glucose concentration, hemoglobin, RBC and reticulocyte count, and the calculated percentage of RBC count represented by reticulocytes were determined monthly for at least 12 months (range, 12 to 26 months) in 48 adults (mean age, 51 years; range, 31 to 82 years). In 37 of the subjects, RBC survival using a CO method also was determined. There was a highly significant linear correlation between the fasting glucose concentration and the tGHb. There was only a weak correlation between the percent reticulocytes or with the RBC survival determined by the CO method. The tGHb, plasma glucose, RBC count, hemoglobin, and percent reticulocytes were very stable over a 12-month or greater period. We conclude that there is a good correlation between the tGHb and plasma glucose concentration in a population without known diabetes. Variations in RBC survival as indicated by a reticulocyte count within the reference range is not likely to have a clinically significant effect on interpretation of tGHb data in the context of an integrated glucose concentration. Nevertheless, this remains to be proven using RBC survival methods that are more precise than those currently available.