Because sleep is known to reduce ventilatory drive, and sleep deprivation is a common accompaniment to ventilatory failure, we tested ventilatory response to carbon dioxide (delta V1/delta PCO2) and response to an inspiratory flow resistive load (change in delta P100/delta PCO2 with load) after both a normal night of sleep and after 24 hours of sleep deprivation in 13 healthy volunteers. Sleep deprivation was associated with a significant decrease in delta V1/delta PCO2 from 2.51 +/- .36 to 2.09 +/- .34 L/min/mm Hg (p less than 0.02). However, load compensation was preserved during sleep deprivation. Since many acutely-ill patients are sleep deprived, an associated reduction of ventilatory drive may play a role in progressive respiratory insufficiency.