To evaluate relative contributions of inherent versus extrinsic factors to respiratory chemosensitivity, ventilatory responses to isocapnic progressive hypoxia and normoxic progressive hypercapnia were examined at intervals of 8 to 10 yr in 32 healthy male volunteers aged 42.2 +/- 1.4 yr (SEM) in the final examination. The volunteers included 22 sons of patients with chronic obstructive pulmonary disease. The mean value for the slope factor of the end-tidal PO2-ventilation hyperbola (A) significantly decreased from 98.3 +/- 12.2 to 77.4 +/- 10.3 L/min mm Hg (p less than 0.05), but that for the end-tidal PCO2 ventilation line (S) did not change over the years. The individual values for the hypoxic ventilatory response were significantly correlated (r = 0.63, p less than 0.001) between the initial and final examinations but not so for the hypercapnic ventilatory response (r = 0.23, NS), suggesting that the latter is more subject to influence from extrinsic factors than the former in the long term. The reproducibility of both tests expressed as coefficients of variation was similar or rather small for the hypercapnic ventilatory response, which was determined by three consecutive measurements at 1 wk intervals in a different group of six subjects. From these data we conclude that hypoxic chemosensitivity is more determined by factors inherent to the individual than hypercapnic chemosensitivity and that it is more systematically influenced by temporal factors, as demonstrated by the systematic decrease over the years.