This study investigated the associations between serum C-reactive protein and fasting blood levels of insulin, glucose, and hemoglobin A1c (HbA1c). Data from the Third National Health and Nutrition Examination Survey (1998-1994) were used. Study subjects included 2,466 men and 2,876 women who were > or = 17 years and nondiabetics with an overnight fast for blood draw. C-reactive protein was categorized into low (<0.3 mg/dl), moderate (0.3-0.9 mg/dl), and high (> or = 1.0 mg/dl) levels. Mean levels of insulin, glucose, and HbA1c were compared across C-reactive protein levels after adjustment for age, ethnicity, education, poverty index, cigarette smoking, alcohol use, and leisure time physical activity. For men with low (n = 1,818), moderate (n = 493), and high (n = 155) C-reactive protein, the adjusted means of insulin were 9.4, 11.7, and 10.5 microunits/ml (p < 0.01); glucose, 99.8, 101.6, and 100.6 mg/dl (p > 0.05); and HbA1c, 5.4%, 5.5%, and 5.5% (p < 0.05). For women with low (n = 1,816), moderate (n = 776), and high (n = 282) C-reactive protein, the adjusted means of insulin were 8.7, 11.2, and 13.7 microunits/ml (p < 0.01); glucose, 95.3, 97.9, and 105.2 mg/dl (p < 0.01); and HbA1c, 5.3%, 5.4%, and 5.6% (p < 0.01). In conclusion, elevated C-reactive protein was associated with higher insulin and HbA1c among men and women and with higher glucose levels among women only. These results suggest a possible role of inflammation in insulin resistance and glucose intolerance.