C-reactive protein (CRP) is a marker for systemic inflammation and increased cardiovascular disease risk. Regular exercise may decrease CRP. Apolipoprotein E (apo E) has 3 common genotype variants--E2/3, 3/3, and 3/4--that modulate lipid metabolism and may have other metabolic physiologic roles, including some evidence that the genotype affects CRP levels. We assessed fasting serum CRP in 117 (male = 51, female = 66) healthy adults who volunteered for a 6-month aerobic exercise program. Both pre- and posttraining measurements were available in 71 (male = 31, female = 40) subjects. At baseline and follow-up, the numbers of subjects in the 3 groups were approximately equal: 2/3, n = 33 and 20; 3/3, n = 41 and 26; and 3/4, n = 43 and 25. At baseline, CRP levels differed by apo E genotype: means +/- SD were 2.84 +/- 2.18, 2.59 +/- 2.34, and 1.90 +/- 2.13 mg/L for E2/3, 3/3, and 3/4 subjects, respectively (3/4 vs 2/3, P < .05). In women, CRP was higher than that in men (3.14 +/- 2.49 vs 2.12 +/- 2.13 mg/L, P < .006). Exercise failed to affect CRP in the entire cohort (2.68 +/- 2.38 vs 2.52 +/- 2.48 mg/L) or in any apo E genotype group, and the apo E genotype effect observed at baseline persisted after training. In a largely white study cohort, CRP is higher in apo E3/3 than in 3/4 subjects and in women compared with men, but remains unchanged by 6 months of standard aerobic exercise training of the volume and higher intensity promoted by national organizations to reduce cardiovascular disease risk. How apo E genotype affects CRP is not known.