Regular physical activity is considered to be part of a modern healthy life style, and is widely recommended by both the medical community and clinical guidelines for the prevention and management of cardiovascular (and other) disorders (1). This general confidence in the health benefits of physical training is based on numerous epidemiological studies and other clinical evidence indicating that regular exercise may delay the development of atherosclerosis and reduce the incidence of coronary artery disease (1). Indeed, one meta-analysis has demonstrated that the relative risk of death from coronary artery disease for sedentary compared with active individuals was increased 1.9-fold (95% confidence interval 1.6–2.2) (2). Nonetheless, not every sort of physical activity can be considered equally beneficial or even safe. Indeed, various reports demonstrate that vigorous physical training can transiently increase the risk of acute myocardial infarction and sudden cardiac death in susceptible individuals (1). Some cardiovascular conditions, such as atrial fibrillation, are more prevalent amongst habitual long distance runners (3) and – of course – an ‘athelete’s heart syndrome has been well described (4). More intensive types of activity, such as jogging appear to carry a certain risk of unfavourable cardiovascular events (5). For example, in the Rhode Island study of the middle-aged men, despite the low overall incidence of death during jogging per se (that is, one death per year for every 7,620 joggers) this risk was still seven-fold higher when compared to individuals with more sedentary activities (5). Which factors mediate the shift from beneficial effects of less intensive exercise regimes to potentially dangerous consequences of more intensive types of activity? Undoubtedly, these processes are complex and include numerous aspects, not all of which are entirely understood (6). For example, physical activity modulates the state of the coagulation system triggering either proor anti-thrombotic changes, depending upon the intensity and regularity of the training (7, 8). Also, the systemic and local (i.e. vascular) inflammatory status could perhaps represent one of many pathophysiological pathways (9–11). Indeed, an increased risk of developing cardiovascular disease, obesity, and diabetes with a sedentary lifestyle has been associated with a low-grade inflammatory status (12, 13). In a study of 1,383 asymptomatic individuals, for example, monocyte counts had the strongest independent relationship with overall cardiovascular risk, and other independent associations have been demonstrated between monocyte count and several cardiovascular risk factors such as blood pressure, body mass index, waist circumference, high-density lipoprotein (HDL) cholesterol and triglyceride levels (14). However there is a possibility that the functionality of monocytes themselves may be of importance. Several studies have reported that monocyte expression of tolllike receptor-4 (TLR4, an endotoxin receptor) and their antigen-presenting capacity can be temporarily reduced by acute bouts of strenuous exercise. These observations indicate that such unusually intensive episodes of physical activity may perhaps be associated with an acute inflammatory reCorrespondence to: Dr. Eduard Shantsila University of Birmingham Centre for Cardiovascular Sciences City Hospital, Dudley Road Birmingham, B18 7QH, UK Tel.: +44 121 5075080, Fax: +44 121 554 4083 E-mail: e.shantsila@bham.ac.uk