10.1152/japplphysiol.00630.1999.Some recent studies of competitive athletes have shown exercise-induced hypoxemia to begin in submaximal exercise. We examined the role of ventilatory factors in the submaximal exercise gas exchange disturbance (GED) of healthy men involved in regular work-related exercise but not in competitive activities. From the 38 national mountain rescue workers evaluated (36 ± 1 yr), 14 were classified as GED and were compared with 14 subjects matched for age, height, weight, and maximal oxygen uptake (O_2 max; 3.61 ± 0.12 l/min) and showing a normal response (N). Mean arterial PO₂ was already lower than N (P = 0.05) at 40% O_2 max and continued to fall until O_2 max (GED: 80.2 ± 1.6 vs. N: 91.7 ± 1.3 Torr). A parallel upward shift in the alveolar-arterial oxygen difference vs. %O_2 max relationship was observed in GED compared with N from the onset throughout the incremental protocol. At submaximal intensities, ideal alveolar PO₂, tidal volume, respiratory frequency, and dead space-to-tidal volume ratio were identical between groups. As per the higher arterial PCO₂ of GED at O_2 max, subjects with an exaggerated submaximal alveolar-arterial oxygen difference also showed a relative maximal hypoventilation. Results thus suggest the existence of a common denominator that contributes to the GED of submaximal exercise and affects the maximal ventilatory response.