Systemic O-2 transport during maximal exercise at different inspired PO2 (PIO2) values was studied in sodium cyanate-treated (CY) and nontreated (NT) rats. CY rats exhibited increased O-2 affinity of Hb (exercise O-2 half-saturation pressure of Hb = 27.5 vs. 42.5 Torr), elevated blood Hb concentration, pulmonary hypertension, blunted hypoxic pulmonary vasoconstriction, and normal ventilatory response to exercise. Maximal rate of convective O-2 transport was higher and tissue O-2 extraction was lower in CY than in NT rats. The relative magnitude of these opposing changes, which determined the net effect of cyanate on maximal O-2 uptake ((V) over dot O-2max), varied at different PIO2: (V) over dot O-2max (ml.min(-1).kg(-1)) was lower in normoxia (72.8 +/- 1.9 vs. 81.1 +/- 1.2), the same at 70 Torr PIO2 (55.4 +/- 1.4 vs. 54.1 +/- 1.4), and higher at 55 Torr PIO2 (48 +/- 0.7 vs. 40.4 +/-: 1.9) in CY than in NT rats. The beneficial effect of cyanate on (V) over dot O-2max at 55 Torr PIO2 disappeared when Hb concentration was lowered to normal. It is concluded that the effect of cyanate on (V) over dot O-2max depends on the relative changes in blood O-2 convection and tissue O-2 extraction, which vary at different PIO2. Although uptake of O-2 by the blood in the lungs is enhanced by cyanate, its release at the tissues is limited, probably because of a reduction in the capillary-to-tissue PO2 diffusion gradient secondary to the increased O-2 affinity of Hb.