Urea and trimethylamine oxide (TMAO), the major osmolytes in the body fluids of marine elasmobranch fishes, are known to exert counteracting effects on the functions of a variety of enzymes and other proteins of vertebrates (cf. Yancey et al., '82). Although urea raises the O2 affinity of the hemoglobin (Hb) of Squalus acanthias and reduces its sensitivity to the major allosteric cofactor, ATP, the oxygenation reactions of the Hb are insensitive to TMAO, reflecting the absence of urea-TMAO counteraction in the absence or in the presence of the phosphate.