The ventilatory response to moderate exercise is potentiated during hypoxia in goats, causing PaCO2 to decrease more from rest to exercise than in normoxia. We investigated the hypothesis that this response is due to the ventilatory stimulus provided by an interaction between exercise induced hyperkalemia and hypoxia. Plasma potassium concentration ([K+]), arterial blood gases and ventilation were measured in normoxia and hypoxia (PaO2 = 34-38 Torr) at rest and during steady-state exercise (5.6 kph; 5% grade) in seven goats. PaCO2 decreased during normoxic exercise (2.9 +/- 0.7 Tor; P less than 0.01), and decreased significantly more during hypoxic exercise (6.4 +/- 0.6 Torr; P less than 0.01). [K+] increased in both normoxic (1.0 +/- 0.1 mEq/L; P less than 0.01) and hypoxic (0.9 +/- 0.2 mEq/L; P less than 0.01) exercise, but these changes were not significantly different from each other. On a different day, resting goats were infused intravenously with 200 mM KCl for 5 min at a rate sufficient to obtain [K+] similar to exercise (8.6-12 ml/min) in normoxia and hypoxia. Hyperkalemia at rest caused similar PaCO2 decreases in normoxia (1.7 +/- 0.7 Torr; P less than 0.05) and hypoxia (1.7 +/- 0.5 Torr; P less than 0.01), but had no statistically significant effect on ventilation in either condition. These data indicate that hyperkalemia, at levels approximating those during moderate exercise, has a mild stimulatory effect on alveolar ventilation; however, hypoxia does not affect this response. We conclude that hyperkalemia does not provide sufficient ventilatory stimulation to account for exercise hyperpnea, nor does hypoxia potentiate the ventilatory stimulation from hyperkalemia at rest.