In the doubly labeled water (DLW) method, for measurement of energy ex
penditure in humans, calculation of carbon dioxide production rate is
influenced by the ratio (R) of the dilution spaces of the tracer isoto
pes H-2 and O-18. Recent publications have recommended use of a fixed
value for R, using a mean population value ((R) over bar) rather than
individually derived experimental values. However, most of the data co
nsidered previously were derived from adults. Infants are characterize
d by rapid rates of energy deposition and high body water content, eit
her of which could influence isotope kinetics. We have considered whet
her use of a fixed R value is suitable for DLW studies of infants, and
whether the adult (R) over bar value is appropriate. Data from 281 DL
W measurements in healthy infants aged 6 wk to 12 mo were analyzed. Me
an R of all measurements was 1.036 (SD 0.019), very similar to (R) ove
r bar values recommended for adults. We found analytical precision cou
ld account for almost all between-subject variation at a single time p
oint. However, we also found relationships between R and age and weigh
t gain, indicating that physiology does influence the space ratio. The
effect of weight gain on R was negligible, but changes of (R) over ba
r with age, reflecting changes in percentage body water during infancy
, were of sufficient magnitude to affect calculation of energy expendi
ture significantly. Our analysis suggests that use of a fixed ratio at
a single time point in infancy is acceptable, but that the appropriat
e value of R- changes over the first year of life.