The 'open window' theory is characterised by short term suppression of the immune system following an acute bout of endurance exercise. This window of opportunity may allow for an increase in susceptibility to upper respiratory illness (URI). Many studies have indicated a decrease in immune function in response to exercise. However many studies do not indicate changes in immune function past 2 hours after the completion of exercise, consequently failing to determine whether these immune cells numbers, or importantly their function, return to resting levels before the start of another bout of exercise. Ten male 'A' grade cyclists (age 24.2 +/- 5.3 years; body mass 73.8 +/- 6.5 kg; VO2peak 65.9 +/- 7.1 mL x kg(-1) x min(-1)) exercised for two hours at 90% of their second ventilatory threshold. Blood samples were collected pre-, immediately post-, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours post-exercise. Immune variables examined included total leukocyte counts, neutrophil function (oxidative burst and phagocytic function), lymphocyte subset counts (CD4+, CD8+, and CD16+/56+), natural killer cell activity (NKCA), and NK phenotypes (CD56dimCD16+, and CD56(bright)CD16-). There was a significant increase in total lymphocyte numbers from pre-, to immediately post-exercise (p < 0.01), followed by a significant decrease at 2 hours post-exercise (p < 0.001). CD4+ T-cell counts significantly increased from pre-exercise, to 4 hours post- (p < 0.05), and 6 hours post-exercise (p < 0.01). However NK (CD16+/56+) cell numbers decreased significantly from pre-exercise to 4 h post-exercise (p < 0.05), to 6 h post-exercise (p < 0.05), and to 8 h post-exercise (p < 0.01O). In contrast, CD56(bright)CD16- NK cell counts significantly increased from pre-exercise to immediately post-exercise (p < 0.01). Neutrophil oxidative burst activity did not significantly change in response to exercise, while neutrophil cell counts significantly increased from pre-exercise, to immediately postexercise (p < 0.05), and 2 hours post-exercise (p < 0.01), and remained significantly above pre-exercise levels to 8 hours post-exercise (p < 0.01). Neutrophil phagocytic function significantly decreased from 2 hours post-exercise, to 6 hours post- (p < 0.05), and 24 hours post-exercise (p < 0.05). Finally, eosinophil cell counts significantly increased from 2 hours post to 6 hours post- (p < 0.05), and 8 hours post-exercise (p < 0.05). This is the first study to show changes in immunological variables up to 8 hours post-exercise, including significant NK cell suppression, NK cell phenotype changes, a significant increase in total lymphocyte counts, and a significant increase in eosinophil cell counts all at 8 hours post-exercise. Suppression of total lymphocyte counts, NK cell counts and neutrophil phagocytic function following exercise may be important in the increased rate of URI in response to regular intense endurance training.