In an attempt to produce in vivo alterations in the affinity of hemoglobin for oxygen by pharmacologic means, rhesus monkeys were infused with 20 ml/kg of a 0.1 M solution of inosine, pyruvate, and bisodium phosphate. Control monkeys received equal volumes of isotonic saline. The monkeys given the inosine-pyruvate-phosphate mixture demonstrated a mean rise in P50 from 33.5 to 36.1 mm Hg and an increase in mean red cell 2, 3-diphosphoglycerate levels from 5.1 to 7.6 µmoles/ml RBC. The changes were maximal 6 hr postinfusion, remained elevated for 24 hr, and then gradually returned to normal over a 4-day period. Inosine alone, or pyruvate and phosphate together failed to produce the same results. This finding indicates that intravenous administration of inosine, pyruvate and phosphate can alter oxygen affinity in vivo and may be of value in diseases associated with poor oxygen delivery to tissues.