Long distance running has been shown to increase pro-inflammatory cytokines and cytokine-inhibiting reactions, which also effects metabolism and cardiovascular regulation. However, the dose-responses of such processes are not sufficiently understood yet. PURPOSE To compare the immediate impact of distinct bouts of long distance running on TNF-α, TNF-α receptor 1 (TNF-α R1), TNF-α receptor 2 (TNF-α R2), and the ratio TNF-α R2: TNF-α R1. METHODS 6 male runners were randomly assigned to a trail-marathon (M) (44 ± 11.5 yrs, 176.8 ± 9.8 cm, 69 ± 10 kg) and a trail-10 km (K) (43 ± 10 yrs, 179.2 ± 1.5 cm, 77 ±2.7 kg). Venous blood samples were collected before and immediately after the run for measurements of TNF-α, TNF-α R1, and TNF-α R2, haemoglobin and haematocrit. Heart rate was monitored throughout the race. RESULTS Average running time was 4.5 times longer in the M compared to the K (270 ± 77 vs. 59 ± 1 min, t = 4.7, p <0.005), however running intensity as indicated by average heart rate was not significantly different between the M and the K (143 ± 8.3 vs. 139 ± 24 bpm, p >0.05). There was no significance differences in pre and post-race levels of haemoglobin in M (137.7 ± 9.1 vs. 145.7 ± 3 g.l−1, p >0.05), or K (145.7 ±11.2 vs. 149 ± 9.5 g.l−1, p >0.05). There was no significance difference in the pre and post-race haematocrit in M (41.7 ±2.1 vs. 41±1.7%, p>0.05), or K (41.3 ±1.1 vs. 41.7 ± 1.5 %, p >0.05). There was a significant reduction in TNF-α between pre and post samples among M (100.6 ± 17.2 vs. 93 ± 19.5 pg·ml−1, t = 2.9, p <0.05), but not among K (103.6 ± 94.3 vs. 105 ± 136 pg·ml−1, p >0.05). There was a significant increase in TNF-α R1 between pre and post samples among M (0.74 ± 0.25 vs. 1.7 ± 0.41 ng.ml−1, t = −10.4, p <0.005), and among K (0.67 ±0.04 vs. 1.07 ±0.05 ng.ml−1, t =−7.9, p <0.01). There was a significant increase in TNF-α R2 between pre and post samples among K (1.55 ± 0.39 vs. 1.84±0.45 ng.ml−1, t = −7.4, p <0.01), but not among M (1.47 ± 0.15 vs. 1.9 ± 0.22 ng.ml−1, p >0.05). There was a significant reduction in the ratio TNF-α R2: TNF-α R1 between pre and post samples among M (2.09 ±0.45 vs. 1.17 ± 0.35, t= 14.1, p <0.005), and among K (2.33 ± 0.69 vs. 1.71 ± 0.36, p <0.05). CONCLUSIONS The present results extend previous findings of different time courses in exercise related changes of the TNF-α R1, and TNF-α R2. They may serve as a hint for differences in the dose response of the TNF-a R1 and the TNF-α R2 with respect to the volume and the intensity of exercise.