The purpose of this study was: (1) to identify the determinants of the hypercapnic (HCR) and hypoxic response (HR) in normal man; (2) to find out if they are dependent on the HR model used; and (3) to investigate if the occlusion pressure (P0.1), in contrast to the VE HCR and HR, is independent of gender, anthropometrical and lung functional indices. A total of 26 men (42.4+/-12.4 years) and 25 women (40.1+/-13.7 years) were studied. We found that men and women have similar P0.1 respiratory drives, but VE differs and is higher in men because of their larger vital capacity. For comparisons of the HCR or HR either the P0.1, or the VE HCR and HR normalized for VC or FEV1 should be used. With advanced age the VE HCR decreases in women. Especially for the HR, the identification of determinants (including age) is dependent on the HR model used.