Mechanisms underlying the circadian rhythm in lung ventilation were investi
gated. Ten healthy male subjects were studied for 36 h using a constant rou
tine protocol to minimize potentially confounding variables. Laboratory lig
ht, humidity, and temperature remained constant, subjects did not sleep, an
d their meals and activities were held to a strict schedule. Respiratory ch
emoreflex responses were measured every 3 h using an iso-oxic rebreathing t
echnique incorporating prior hyperventilation. Subjects exhibited circadian
rhythms in oral temperature and respiratory chemoreflex responses, but not
in metabolic rate. Basal ventilation [i.e., at subthreshold end-tidal carb
on dioxide partial pressure (PETCO2)] did not vary with time of day, but th
e ventilatory response to suprathreshold PETCO2 exhibited a rhythm amplitud
e of similar to 25%, mediated mainly by circadian variations in the CO2 thr
eshold for tidal volume. We conclude that the circadian rhythm in lung vent
ilation is not a simple consequence of circadian variations in arousal stat
e and metabolic rate. By raising the chemoreflex threshold, the circadian t
iming system may increase the propensity for respiratory instability at nig
ht.