To determine the influence of prolonged nicotine exposure on maximal physical working capacity, a study of clinical measures of physical fitness and cardiovascular response to exercise was performed in 144 healthy men, 35-60 years old, subdivided into smokeless tobacco users, smokers and non-users of tobacco. Regular users of smokeless tobacco, with exposures of more than 20 years, showed similar maximal oxygen uptake (mean 3.48 L min-1, SD 0.49, n = 48) to non-users (mean 3.51 L min-1, SD 0.51, n = 65). In smokeless tobacco users, higher blood pressure and heart rate values were observed at rest and at submaximal work, after exposure to tobacco shortly before the exercise test, but not at maximal work. However, significantly lower maximal oxygen uptake was found for smokers (mean 2.88 L min-1, SD 0.49, n = 31) compared with non-users (P < 0.001). Plasma concentration of continine, the main metabolite of nicotine, was significantly higher in smokeless tobacco users (mean 347 ng mL-1, SD 175, n = 48) than in smokers (mean 253 ng mL-1, SD 153, n = 31, P < 0.001). The findings indicate that long-term use of smokeless tobacco does not significantly influence exercise capacity in healthy, physically well-trained subjects.