The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O2 consumption (V̇O2,max) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 ± 0.6 years, mean ±s.e.m.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2-4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O2 in N2) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V̇O2,max, showing that breathing ambient air at 5260 m, V̇O2,max is limited by the availability of O2 rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 ± 5 to 185 ± 5 g l−1 (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 ± 6 g l−1 (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V̇O2,max, or power output. Despite higher LBF, leg O2 delivery was reduced and maximal V̇O2 was thus maintained by higher O2 extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (FI,O2), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K+ concentrations, independently of [Hb] and FI,O2. In summary, under conditions where O2 supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V̇O2,max, and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V̇O2,max may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.