Some patients with lung disease retain CO2, while others with similar lung function do not. This could be explained if CO2 retainers had a pre-existing low hypercapnic ventilatory response (HCVR) and, from this, a tendency to retain CO2. To test if such a phenomenon exists in healthy people, we determined the change in end-tidal PCO2 (?PETCO2) produced by the addition of a dead-space (DS), during wakefulness and sleep, and related this to the HCVR measured awake. The group mean (n=14) HCVR slope was 2.2ᱮ1 (S.D.) L min-1 mmHg-1. The ?PETCO2 with the application of DS was 1.6ᱮ6 mmHg awake and 2.6Ხ2 mmHg asleep. During wakefulness the ?PETCO2 with DS did not correlate with the HCVR slope. However, during sleep, four subjects had a marked increase in the ?PETCO2 (3.7, 4.3, 6.2, 8.0 mmHg) and a relatively low HCVR (slope 1.5, 1.7, 1.5, 1.7 L min-1 mmHg-1, respectively). We speculate that such individuals, should they develop lung disease, may be predisposed to retain CO2.