This study defines the relationship between heart rate and metabolic rate in newborn infants and evaluates the accuracy of prediction of metabolic rate from heart rate. Continuous measurements of oxygen uptake, CO2 production, respiratory quotient, and cumulative heart rate were performed using computerized, open-circuit indirect calorimetry and on-line electrocardiogram monitoring over periods of 1 to 24 hr (mean 4.5 hr). Metabolic rate was calculated from the individual oxygen uptake and respiratory quotient. Thirty-five studies were performed in 16 infants (birthweight 0.75 to 3.1 kg; gestational age, 26 to 42 wk; mean +/- S.D. age at study, 26.5 +/- 15.7 days; study weight, 1.78 +/- 0.5 kg). Metabolic rate (cal/kg . min) and heart rate (beats/min) were compared minute by minute (8269 measurements) and showed a close third degree polynomial relationship for heart rates of 110 to 230/min (y = -0.0000291x3 + 0.01685x2 -2.93x + 197; r = 0.99; P less than 0.001); however, at heart rates above 140 beats/min, a linear relationship was found (r = 0.997; P less than 0.001). From cumulated heart rate measurements, factors defining metabolic rate per heart beat were also determined: for each beat 51.8 +/- 6.8 microliter of oxygen/kg are consumed and 0.258 +/- 0.03 cal/kg (1.1 J/kg) are expended. Despite the wide variation in birthweight, gestational age, method of feeding, and clinical characteristics, there was a remarkable consistency in the heart rate-metabolic rate relationships. A further 10 studies were performed in a similar group of infants to assess the predictive value of the previously defined relationships and showed a mean percentage deviation of 5.7 +/- 4% from the measured value. We conclude that in the varied group of newborns studied, heart rate correlates closely with metabolic rate and that cumulative heart rate measurements enable the estimation of metabolic rate in newborn infants. This provides a method of monitoring energy expenditure and caloric requirements over long periods.