A prospective trial was conducted with 14 hospitalized patients who were severely underweight with a mean weight of 40.9+/-5.1 kg and 70.7+/-7.8% of ideal body weight, to compare estimates of resting energy expenditure (REE) with measured values. The 9 women and 3 men, whose mean age was 66.5+/-13.9 y, underwent nutritional assessment and measurement of their REE by indirect calorimetry using the Sensormedics Deltatrac MBM100 indirect calorimeter. Their REE was also estimated by the Harris-Benedict formula (mean 1032+/-66 kcal/d) as well as a previously established empirical formula where REE = 25 x body weight in kg (mean 1023+/-129 kcal/d). Results by both estimates were significantly lower than the measured resting energy expenditure (MREE) in this group of patients (P<0.0001). The percentage difference between MREE and estimated REE by the Harris-Benedict formula was 18.4+/-9.4% and 20.9+/-7.5% by the empirical formula. The MREE exceeded the estimated REE in each individual. The correlation between MREE and body weight (r2 = 0.558, r = 0.005) was better than that between MREE and estimated REE by Harris-Benedict formula (r2 = 0.275, P = 0.08) suggesting that weight was the principal determinant rather than the other components (height, age, sex) of the Harris-Benedict formula. Our data shows that commonly employed formulae routinely underestimate the energy needs of severely underweight patients below 50 kg in body weight. The Harris-Benedict equation had limited predictive value for the individual, explaining approximately 25% of the variance in energy expenditure. Given the particular importance of matching energy intake to needs in this group of patients with limited reserves, many of whom are critically ill, we suggest an empirical equation using 30-32 kcal/kg be used to estimate the energy requirements of severely underweight patients when direct measurements are unavailable or clinically less imperative.