The malnutrition common among patients with ALS can be attributed in some cases to increased resting energy expenditure (REE). However, the origins and evolution of this hypermetabolism have yet to be fully elucidated. The aim of the present study was to monitor REE over time in patients with ALS and to identify factors that may explain any variation observed. ALS patients underwent nutritional, neurological and respiratory assessment every 6 months for 2 years (or until they died or became physically incapable of being examined). Sixty-one patients were studied. At inclusion, 47.5% exhibited hypermetabolism, with a mean measured REE (mREE) 19.7 +/- 6.4% higher than the mean calculated REE (cREE) (P < 0.0001). The hypermetabolism persisted when mREE was normalized for fat free mass (FFM): 35.1 +/- 4.2 versus 32.3 +/- 4.7 kcal/kg day(-1) (P = 0.02) in hypermetabolic and normometabolic patients, respectively. In univariate analysis, mREE was negatively correlated with age and positively correlated with BMI, FFM, energy and protein intakes, and albumin level. No correlation was found with neurological scores, disease characteristics, respiratory function and survival. Multivariate analysis revealed no significant factors. Only 10 of 45 patients in whom REE was measured at least twice changed their metabolic status. Neither mREE nor mREE/cREE varied significantly over time, despite deteriorating neurological, nutritional and respiratory parameters (P < 0.0001), and an increase in mREE/FFM (P = 0.01). This study confirms that about 50% of ALS patients are hypermetabolic, and 80% show no change in metabolic status over time. Thus, metabolic status (a clinically useful indicator of the need for nutritional support) can be determined early in the evolution of the disease. The origin of hypermetabolism in this context remains unknown, but growing evidence points to mitochondria as having an important role.