To investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.We assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (PAO2) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.Fasting serum glucose was not significantly different between the men with AIDS (87 +/- 4 mg/dL) and the healthy male volunteers (84 +/- 6 mg/dL); however, A1C (6.9 +/- 0.2%) and serum fructosamine levels (288 +/- 15 micromol/L) were significantly higher (P<.01) in the patients with AIDS than in the normal subjects (A1C, 5.6 +/- 0.1%; fructosamine, 204 +/- 14 micromol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P<.01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin <12 g/dL) or hypoxia (PAO2 <95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 +/- 3 mg/L) and the normal subjects (22 +/- 4 mg/L).On the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent.