Background: Lactose malabsorption occurs frequently and the variable consequent intolerance may seriously impair quality of life. No reliable and convenient test method is in routine clinical practice. A recent animal study showed that the respiratory quotient changed significantly after ingestion of sucrose and lactose in naturally lactase-deficient rats. Aims: This exploratory study evaluated the relevance of monitoring the respiratory quotient after lactose ingestion to detect malabsorption. Methods: Healthy volunteers were identified and classified lactose absorbers and malabsorbers by a lactose tolerance test (25 g). After an overnight fast, a second lactose challenge was performed to monitor hydrogen excretion and respiratory quotient kinetics over 4 h. Participants also completed questionnaires to score and localise their gastrointestinal symptoms. Results: 20 subjects were enrolled (10 per group, 60% males, mean age 34 +/- 4 years). Respiratory quotient kinetics were different between absorbers and malabsorbers during the first 100 min after lactose ingestion (p \textless 0.01) and during the initial 30-50 min period. Respiratory quotient was significantly, positively correlated to peak glycaemia (R = 0.74) and negatively correlated to hydrogen excretion (R = -0.51) and symptoms score (R = -0.46). Conclusions: Indirect calorimetry could improve the reliability of lactose malabsorption diagnosis. Studies on larger populations are needed to confirm the validity of this test and propose a simplified measurement. (c) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.