Interleukin 6 (IL-6) response was studied during two ultra endurance events-one laboratory 24 h protocol (9 men) with exercise intensity set to 60% of VO(2max) and one Adventure Race over 6 days (12 men/6 women) with a self-selected race pace, including rests, of about 38% of VO(2max). In the 24-h protocol IL-6 level was elevated from 0.76 ± 0.48 pg mL(-1) at rest to 7.16 ± 2.70 pg mL(-1) at 6 h, and increased further to 10.58 ± 1.04 pg mL(-1) at 12 h, but remained thereafter unchanged at 24 h, (10.89 ± 0.36 pg mL(-1)). All participants had nearly identical values at 12 and 24 h, supporting intensity as main determinant in the IL-6 response during prolonged exercise since exercise duration did not increase IL-6 level after 12 h. Possible confounding factors do not seem to influence the IL-6 concentration during the longer races (>12 h), but might very well do so during shorter exercise bouts. In the 6-day race IL-6 increased from rest to 24 h, but thereafter there was no change in plasma IL-6 value until the end of the race (mean 143.5 h). There was no elevation of TNF-α in any of the protocols, suggesting that the competitors were free from systemic inflammation. We conclude that during endurance exercise lasting >12 h intensity, and not duration, is the main determinant of the IL-6 response, while during shorter exercise bouts both intensity and duration contribute to the accumulation of IL-6 in plasma.