Effects of ionic (Hypaque-76) and nonionic (Isovue-370 and Omnipaque-350) contrast media on oxyhemoglobin dissociation of normal human red blood cells were evaluated. In series 1, 4-mL venous blood samples were obtained from 15 normal human volunteers. One blood sample served as control, and 1 mL of either of the three contrast media was added in vitro to the other 4-mL blood samples. P50 values were estimated from the linear portion of the oxyhemoglobin dissociation curve obtained by tonometry. Determinations of P50 were performed at either pH 7.4 or 7.2. At pH 7.4, P50 in the absence of contrast media was 26.3 +/- 0.4 mm Hg (mean +/- SEM). The contrast media caused comparable decreases in P50 from this value (Hypaque-76, 20.0 +/- 0.5 mm Hg; Omnipaque-350, 21.6 +/- 0.4 mm Hg; Isovue-370, 20.7 +/- 0.4 mm Hg). Reducing pH to 7.2 in the absence of contrast media increased P50 to 33.3 +/- 1.0 mm Hg, evidence of the Bohr effect. The presence of contrast media either completely abolished (Hypaque-76 and Omnipaque-350) or markedly attenuated (Isovue-370) this effect. In series 2 (five patients), blood samples were withdrawn from the external iliac artery during injection of Isovue-370 (60-78 mL) into the proximal abdominal aorta to evaluate peripheral vascular disease. Measurement of P50 of these samples yielded findings consistent with those of series 1. The present findings demonstrate that both ionic and nonionic contrast media increase the affinity of hemoglobin for oxygen and, therefore, that they may inhibit oxygen delivery to body tissues.