We tested the hypotheses that inhibition of nitric oxide (NO) formation reduces maximal O₂ delivery to muscle, therefore lowering maximal O₂ consumption. To test these hypotheses, swine (~30 kg) drank either tap water (Con, n=25) or water with NG-nitro-L-arginine methyl ester (8.0 ± 0.4 mg/kg/d for 4 wk; LN, n=24). Treatment efficacy was reflected by higher mean arterial pressure and lower plasma NO metabolite concentration in LN than Con (both P<0.05). Swine completed 2 graded treadmill running tests to maximum. In the first test, O₂ consumption was determined, at rest through maximal exercise intensity. O₂ consumption did not differ between groups at rest or at most exercise intensities, including maximum (Con, 40.8 ± 1.8 ml/min/kg; LN, 40.4 ± 2.9; n.s.). In the second test, tissue-specific blood flows were determined using the radiolabelled microsphere technique. At rest, blood flows were lower (P<0.05) in LN compared with Con for a number of tissues, including kidney, adrenal, lung, and several skeletal muscles. During both submaximal and maximal exercise, however, blood flows were similar between Con and LN for all 16 muscles examined; only blood flows to kidney (Con, 99 ± 16 ml/min/100 g; LN, 55 ± 15; P<0.05) and pancreas (Con, 25 ± 7; LN, 6 ± 2; P<0.05) were lower in LN at maximum. Endothelium-dependent, but not –independent, relaxation of renal arterial segments was reduced (P<0.05) in vitro. Thus, exercise-induced increases in muscle blood flows are maintained with chronic inhibition of NO formation and that maximal O₂ consumption is therefore preserved.