To determine whether plasma catecholamine concentrations (a measure of sympathetic nervous activity [SNA]) rise above normoxic levels during exercise with hypoxemia, we exercised seven men for 15 min at three loads that required from 40 to 88% of maximal O2 uptake (VO2max). Subjects breathed room air on one day and 11-12% O2 on another with relative work loads corrected for the 24% fall in VO2max during hypoxemia. Hypoxemia caused large increments in norepinephrine (NE) concentration (radioenzyme technique) to 1.21 +/- 0.20 ng/ml (mean +/- SE), 2.79 +/- 0.38, and up to 5.90 +/- 0.75 (hypoxemia) compared with 0.89 +/- 0.06, 1.66 +/- 0.16, and 3.95 +/- 0.39 in normoxia at the three loads, respectively (P less than 0.001). Epinephrine (E) concentration approximately doubled (P less than 0.001) in hypoxemia at each load when compared with normoxic levels (i.e., 0.10 +/- 0.01 ng/ml, 0.23 +/- 0.03, and 0.46 +/- 0.06 in normoxia). However, hypoxemia did not significantly alter linear relationships between log plasma NE concentration and either heart rate (HR) or percent VO2max utilized, or between HR and percent VO2max. Thus NE concentration, like HR, appeared to reflect relative severity of exercise and overall SNA in both hypoxemia and normoxia. Above 40% VO2max during hypoxemia, circulating NE and E far exceeded levels known to have direct vasoconstrictor and metabolic effects in normoxic humans, but hypoxemia may blunt vasoconstriction in some regions.