Differences in the immune and inflammatory response to exercise between healthy and illness-prone athletes may be one explanation why some athletes experience a greater incidence of upper respiratory symptoms than others. The aim of this study was to compare the C-reactive protein (CRP) response to acute exercise between healthy and illness-prone trained distance runners. Runners were classified as healthy (< or =2 episodes of upper respiratory symptoms per year; n = 10) or illness-prone (> or =4 episodes per year; n = 8) and completed three treadmill running protocols. CRP concentrations were determined prior to and 24 h following each exercise protocol and responses compared between the two groups. Plasma concentrations of Interleukin (IL)-6, IL-8, IL-10 and the IL-1 receptor antagonist (IL-1ra) were also determined immediately, 1 h, 10 h and 24 h post-exercise. The CRP response at 24 h post-exercise was not substantially different between healthy and illness-prone athletes (approximately 2-10%). There were small to moderate correlations between resting CRP concentrations and the peak IL-6 (r = 0.28, P = 0.04), IL-8 (r = 0.31, P = 0.03), IL-10 (r = 0.28, P = 0.05) and IL-1ra (r = 0.30, P = 0.03) concentrations post-exercise. The CRP response to exercise was not useful in distinguishing between healthy and illness-prone athletes. The relationship between resting CRP concentrations and the peak pro- and anti-inflammatory responses to exercise supports the likely involvement of CRP in the complex network regulating exercise-induced inflammatory disturbance.