OBJECTIVE Endurance exercise and hyperthermia are associated with compromised intestinal permeability and endotoxaemia. The presence of intestinal fatty acid-binding protein (I-FABP) in the systemic circulation suggests intestinal wall damage, but this marker has not previously been used to investigate intestinal integrity after marathon running. METHODS Twenty-four runners were recruited as controls prior to completing a standard marathon and had sequential I-FABP measurements before and on completion of the marathon, then at four and 24 h later. Eight runners incapacitated with exercise-associated collapse (EAC) with hyperthermia had I-FABP measured at the time of collapse and 1 hour later. RESULTS I-FABP was increased immediately on completing the marathon (T0; 2593 ± 1373 ng·l-1) compared with baseline (1129 ± 493 ng·l-1; p < 0.01) in the controls, but there was no significant difference between baseline and the levels at four hours (1419 ± 1124 ng·l-1; p = 0.7), or at 24 h (1086 ± 302 ng·l-1; p = 0.5). At T0, EAC cases had a significantly higher I-FABP concentration (15,389 ± 8547 ng.l-1) compared with controls at T0 (p < 0.01), and remained higher at 1 hour after collapse (13,951 ± 10,476 ng.l-1) than the pre-race control baseline (p < 0.05). CONCLUSIONS I-FABP is a recently described biomarker whose presence in the circulation is associated with intestinal wall damage. I-FABP levels increase after marathon running and increase further if the endurance exercise is associated with EAC and hyperthermia. After EAC, I-FABP remains high in the circulation for an extended period, suggesting ongoing intestinal wall stress.