We systematically investigated the quantitative importance of pH and O2 saturation (SO2) of hemoglobin on the solubility coefficients (alpha) for six inert gases: sulfur hexafluoride, N2, ethane, cyclopropane, halothane, and diethyl ether. Measurements of alpha were made at 37 degrees C with SO2 of 0-1.0 and pH of 7.2-7.7 by use of whole blood obtained from three healthy subjects. No significant dependence of alpha on pH was demonstrated for sulfur hexafluoride, N2, halothane, or diethyl ether, but an appreciable augmentation of alpha with increasing pH was found for ethane and cyclopropane. No alpha value obtained for oxygenated blood differed statistically from that for deoxygenated blood. In addition to the basic findings on the effects of pH on alpha values of ethane and cyclopropane with the multiple inert gas elimination technique (data obtained from 22 patients with either interstitial pneumonia or chronic obstructive pulmonary disease), we also found that dependence of alpha on blood pH exerted no significant influence on the recovery of ventilation-perfusion distribution in the lung. We concluded that: 1) pH plays an appreciable role in determining gas solubilities in blood, 2) SO2 is not a decisive factor for gas solubilities in blood, and 3) the influence of various pH values in pulmonary capillaries on inert gas exchange is negligible.