A decrease in functional residual capacity (FRC) during sleep could result in worsening of ventilation distribution contributing to sleep hypoxemia. Therefore the purpose of this study was to determine whether FRC does decrease and to what extent it decreases in normal humans during sleep. Using helium dilution in a closed system we measured FRC in 10 healthy males during wakefulness, stage 2, stages 3–4, and rapid-eye-movement (REM) sleep. Mean FRC decreased from 3.14 +/- 0.01 (SE) liters during wakefulness to 2.95 +/- 0.01 liters in stage 2 sleep. Lowest sleep values were 2.86 +/- 0.01 liters in stages 3–4 and 2.83 +/- 0.01 liters in REM sleep (P less than 0.05 from wakefulness). Although the amount of the decrease in FRC identified during sleep was surely not large enough to impair ventilation distribution in normal humans, this degree of decrease might contribute to the hypoxemia seen in patients with severe airflow limitation.