In this review the effects of carbon monoxide on tissular oxygenation, at doses which are compatible with life, are considered. In a first section the relative CO-O2 affinity (M*) of various O2 carrying proteins is compared; M* is about 220 for hemoglobin, 20-25 for myoglobin and close to unity for cytochrome oxidases. Thus most of the acute CO toxicity should not be considered as due to malfunction of the intracellular respiratory chain. In addition the differences in M* are caused more by the changes in O2 affinity than by those in CO affinity. The second section deals with the changes in the O2 equilibrium curve (OEC) induced by the presence of HbCO in blood, i.e. the hyperbolization of this curve due to the progressive loss of allostery due to the preferential binding of CO to Hb. The functional importance of this phenomenon lies in the fact that the lower part of the OEC is shifted to the left, whereas the upper part is shifted to the right to an extent which depends upon the amount of HbCO. Thus the effects of the so-called CO anemia are considered to be due both to the reduction of functional Hb and to the reduced partial pressure in the hypoxic range of the OEC. The third section presents recent data concerning the effect of HbCO on the VO2max of the isolated gastrocnemius preparation. The results were obtained in hypoxia under conditions where perfusion and arterial O2 content, i.e. O2 delivery, were the same with and without 30% HbCO. The salient finding is a 26% reduction of VO2max under conditions of CO anemia as compared to hypoxia alone. Interestingly, the PO2 of the venous effluent of the muscle is found to be the same in both cases which leads to the interpretation that it is not the reduction of the mean capillary PO2 but rather a decrease of the blood-to-mitochondria O2 conductance which causes the fall in VO2max.