Exercise as a stimulus to induce lymphocyte apoptosis remains controversial. Differences may be due to participant fitness level or the methodology of assessing cell death. Another important issue is the mode of exercise used to induce physiological changes. Treadmill exercise typically induces significant apoptosis in human lymphocytes; however, the effect of cycle exercise is less clear. The 2 main purposes of this study were to assess if cycle ergometer exercise induces similar changes in apoptosis, and to further characterize the morphological method of assessing cell death. Endurance athletes (n = 10; peak oxygen consumption = 55.1 mL.kg-1.min-1) completed a 60-min ride on a cycle ergometer at approximately 80% peak oxygen consumption. Blood samples taken before (PRE) and after (POST) exercise were used to make blood films for apoptotic analysis via the morphological technique. A significant increase was observed in the apoptotic index following cycle exercise (PRE = 7.3 +/- 2%, POST = 12.9 +/- 2%; p < 0.01). On average, it took 42 +/- 9 min to read PRE sample slides, which was significantly longer than the 27 +/- 4 min needed for POST slides (p < 0.01). To our knowledge, this study is the first to report that exercise on the cycle ergometer produces changes in lymphocyte apoptosis. The values measured during this study were about 20% lower than those we have observed following treadmill running, which may be explained by differences in active muscle mass and the resultant physiological stress between the 2 exercise modes. It is likely that cycling may result in reduced immunosuppression, compared with running at the same intensity.