Design: Non-randomized study. Objective: To determine natural killer cell cytotoxic activity (NKCA) to 2-h arm ergometer exercise in persons with spinal cord injuries (SCI) and the underlying mechanism of such response. Setting: University of Occupational and Environmental Health, Japan. Methods: We examined NKCA response to 2-h arm crank ergometer exercise at 60% of maximum oxygen consumption (VO 2max ) in SCI and able-bodied persons. NKCA and plasma concentrations of prostaglandin E 2 (PGE 2 ), adrenaline and cortisol were measured before, during and immediately after the exercise. The study included seven subjects with SCI between Th11 and L4 and six able-bodied persons.Results: NKCA in able-bodied subjects increased (Po0.05) at 60 min of exercise and immediately after the exercise, and remained elevated up to 2 h after exercise. However, NKCA in SCI decreased (Po0.05) immediately after exercise but recovered at 2 h after exercise. Plasma adrenaline in both groups increased significantly (Po0.05) immediately after exercise and returned to baseline level 2 h after the exercise. Plasma cortisol in both groups remained constant throughout the study. In SCI, PGE 2 significantly increased immediately after 2 h exercise and returned to the baseline level 2 h after exercise; however, it remained unchanged during the test in able-bodied subjects. Conclusion: Our results suggested that increase of PGE 2 in SCI partially contributes to NKCA.