To study the effects of a low carbohydrate, isoenergetic diet on pulmonary physiology and sleep behavior, we measured pulmonary functions and respiratory gas exchange and carried out ambulatory electroencephalographic studies after a week's intake of isoenergetic diet containing only 50 g carbohydrate per day in 6 healthy female adult humans in a free-living condition. Compared with their normal intake, during the week of low carbohydrate intake there was a rise in the level of fasting plasma 3-hydroxybutyrate from 0.12 +/- 0.07 (mean +/- SD) to 1.01 +/- 0.40 mmol/L(P less than 0.01, paired t-test); a fall in serum bicarbonate from 26.2 +/- 0.75 to 25.0 +/- 1.41 mmol/L (P less than 0.05) and in serum chloride from 107 +/- 1.3 to 105 +/- 1.8 mmol/L (P less than 0.05). Serum urea rose from 4.3 +/- 0.71 to 5.7 +/- 0.70 mmol/L (P less than 0.01), and serum uric acid from 0.34 +/- 0.08 to 0.39 +/- 0.10 mmol/L (P less than 0.05). Functional residual capacity was increased from 2.07 +/- 0.35 to 2.26 +/- 0.34 L (P less than 0.01). Respiratory gas exchange ratio fell from 0.81 +/- 0.05 to 0.75 +/- 0.04 (P less than 0.05) and partial pressure of expired carbon dioxide reduced from 22 +/- 3.3 to 21 +/- 3.1 mmHg (P less than 0.05). There was a reduction in endogenous carbon dioxide production and arterial carbon dioxide tension. An analysis of ambulatory electroencephalogram showed that REM latency increased from 66 +/- 8 to 111 +/- 38 min (P less than 0.05), with no significant changes in sleep time and stages. These studies show that a low carbohydrate isoenergetic diet is tolerable, influences sleep behavior, reduces carbon dioxide production and respiratory gas exchange ratio, and may be therapeutically useful in patients with hypercapnic respiratory failure.