To investigate the role of energy expenditure in the altered energy balance in cystic fibrosis (CF), total energy expenditure (TEE) was measured by the doubly-labelled water method in 9 clinically well CF infants (body weight 7.3-10.9 kg) without chronic lung disease. CF infants had 25% higher rates of energy expenditure when compared with data derived from measurements of TEE obtained by the same method in 16 healthy infants, matched for age and body weight. Mean TEE (SEM) for CF was 950 (38) kcal, vs 876 (72) kcal for controls matched for age and 758 (46) kcal for controls matched for weight. Although subclinical disease activity cannot be excluded as a determinant of the excess TEE, the possibility of an energy-requiring basic defect is suggested, because further analysis indicated that factors other than body weight, degree of underweight, presence of pancreatic insufficiency, or presence of lung disease were important. Increased TEE may contribute to undernutrition in CF, even in the absence of chronic lung disease.