An intense physical exercise induces an inflammatory reaction as demonstrated by the delayed increase in blood of acute phase proteins and among them of C-reactive protein (CRP). There is also evidence for a diminished acute phase reaction due to regular exercise suggesting a suppression of the inflammatory response through training. With this background CRP was measured by a sensitive enzyme immunoassay under resting conditions before and after 9 months of training in 14 subjects preparing for a marathon with the aim of studying the effect of training on the base-line CRP concentration. The mean distance run per week increased significantly from 31 +/- 9 km at the beginning to 53 +/- 15 km after 8 months of training (p < 0.01). The aerobic capacity rose significantly after training as demonstrated by the increase of running velocity during a maximal treadmill test from 3.82 +/- 0.29 m/s pre-training to 4.17 +/- 0.17 m/s post-training at a blood lactate concentration of 4 mmol/L (p < 0.01). In 10 of 12 runners base-line CRP was diminished after training in spite of a continuous increase of training intensity. The CRP median fell from 1.19 mg/L before to 0.82 mg/L after training (p < 0.05). Since intense physical exercise is known to be associated with an inflammatory reaction of muscles and tendons, the CRP decrease was unexpected. In 2 subjects the CRP concentration rose markedly because of a borrelia infection and a knee injury, respectively. These values were caused by a pathological condition and were not considered for the statistical evaluation. In 10 non-training control subjects the CRP median did not change significantly during the same 9 months period. The decrease of the CRP base-line concentration after training suggests that intensive regular exercise has a systemic anti-inflammatory effect. This is of particular interest with regard to several recent reports confering on the concentration of CRP in plasma a predictive value for the risk of cardiac infarction, venous thrombosis or stroke.