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This study explores the cardiorespiratory and muscular fatigue responses to downhill (DR) vs uphill running (UR) at similar running speed or similar oxygen uptake (⩒O2). Eight well-trained, male, trail runners completed a maximal level incremental test and three 15-min treadmill running trials at ±15% slope i) DR at ~6 km·h-1 and ~19% ⩒O2max (LDR); ii) UR at ~6 km·h-1 and ~70% ⩒O2max (HUR); iii) DR at ~19 km·h-1 and ~70% ⩒O2max (HDR). Cardiorespiratory responses and spatiotemporal gait parameters were measured continuously. Maximal isomet