Recent research has suggested an association between circulating C-reactive protein (CRP) and adult asthma, confined to those without evidence of allergic predisposition. The current authors investigated the role of smoking and obesity as possible explanations for this relationship. At 44-45 yrs of age, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of the following: CRP; the specific immunoglobulin E to grass, cat and dust mite; standing height; and weight. Information on asthma and related symptoms was collected by computer-aided interview when the subjects were 42 yrs of age. Complete data were available for a total of 6,490 subjects. CRP levels were positively correlated with the body mass index (BMI) and were found to be higher among females when compared with males, and higher among heavy smokers (> or = 20 cigarettes x day(-1)) when compared with never-smokers. After adjustment for sex and region, the odds ratios, comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first quartile, were 1.85 (95% confidence interval 1.15-2.99) for nonatopics and 0.94 (0.62-1.41) for atopics, changing to 1.36 (0.80-2.32) and 1.07 (0.67-1.69), respectively, when additionally adjusted for smoking and BMI. Any association between C-reactive protein and asthma prevalence confined to nonatopics may be due to confounding factors. Alternatively, it may reflect a more general association of C-reactive protein with smoking-related obstructive airways disease.