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 VO2max and one Adventure Race over 6 days (12 men/6 women) with a self-selected race pace, including rests, of about 38 % of VO2max. 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 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 (>12h), 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 (140 h). There was no elevation of TNF-α in any of the protocols, suggesting that the competitors were free from systemic inflammation. 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.