We have shown that normal subjects exercise more efficiently with increased plasma phosphate, presumably due to decreased hemoglobin-oxygen affinity and thus enhanced tissue O2 extraction. We subjected nine stable hypoxemic COLD patients to exercise at 0 (control), 24 (experimental) and 48 hrs (recovery) after phosphate infusion. Baseline variables were identical for each time period. Exercise responses at 0 and 48 hours were also indistinguishable. Exercise response at 24 hrs differed from those at 0 and 48 hours as follows: widening of A-V O2 content difference was more pronounced (28 +/- 6 vs 15 +/- 6 ml/L, p less than 0.03) and the increment in tissue O2 extraction was larger (14 +/- 3 vs 8 +/- 3 percent, p less than 0.03). P50 and related variables did not change during the course of the study. Thus, like normal subjects, hypoxemic patients stimulated with phosphate administration can exercise perhaps more efficiently; but, in contrast to normal subjects, this effect cannot be attributed to changes in hemoglobin-oxygen affinity. These data suggest that phosphate administration may be beneficial in hypoxemic states where adequate tissue oxygenation cannot be achieved by other more conventional methods. The mechanism of this effect remains to be elucidated.