The lumped parameter describing skeletal muscle diffusional conductance for O(2), DM(O(2)), reflects all of the resistances for O(2) in moving from red cell to muscle fiber mitochondria. The purpose of our study was to determine if the carotenoid compound, trans sodium crocetinate (TSC), which has been reported to increase the diffusivity of O(2) in plasma, improves DM(O(2)) and thus, V(O(2),max) in maximally contracting in situ skeletal muscle. V(O(2),max) was measured in the isolated perfused canine gastrocnemius (n=5) during 3 min of isometric tetanic contractions at 1 Hz, while the animal was breathing 12% O(2) (PA(O(2))=32+/-2 Torr, mean+/-S.E.) under two experimental conditions. The first was a control contraction period and the second (following 60 min recovery) was performed within 5 min after infusion of a 0.1 mg x ml(-1) solution of TSC (total dose 100 microg kg(-1)). There were no significant differences in convective O(2) delivery (11.9+/-2.3 vs. 12.1+/-2.2 ml x min(-1) x 100 g(-1)), V(O(2),max) (9.5+/-1.5 vs. 9.6+/-1.5 ml x min(-1) x 100 g(-1)) or calculated DM(O(2)) (0.37+/-0.03 vs. 0.37+/-0.04 ml x min(-1) x 100 g(-1) x Torr(-1)) between contraction periods. As such, our results show that TSC does not improve performance in maximally contracting canine gastrocnemius muscle in situ under moderately hypoxic conditions, suggesting either that TSC in this situation does not increase plasma O(2) diffusivity or that this step in O(2) diffusion from red cell to myocyte does not constrain DM(O(2)).