After being placed on extracorporeal life support (ECLS), newborn patients typically weight 5% to 30% more than their birthweight. Recovery and eventual decannulation from ECLS is associated with a return to baseline weight or birthweight values after a pronounced diuresis. It has been assumed that the increases in weight in these patients are due to increases in extracellular fluid (ECF) and total body water (TBW). This study was undertaken to prove or disprove this hypothesis. ECF space was measured using the compound sodium bromide and TBW was determined with the use of deuterium oxide (nonradioactive heavy water). Fluid compartment measurements were made prior to the institution of ECLS, immediately after placement on bypass, approximately every other day while on bypass, and a final measurement was made once the patient was off bypass. Sodium bromide concentration was analyzed by high-pressure liquid chromatography, and deuterium oxide concentration was measured by the falling drop method. Eight newborns with respiratory failure were placed on either venoarterial (4 patients) or venovenous (4 patients) ECLS for an average of 106 hours (range, 71 to 219 hours). Pre-ECLS TBW was high in the neonates (87% of total body weight v the normal of 75% to 80%). Mean values for each fluid compartment were corrected for the additional volume of the bypass circuit when the patient was on bypass. ECF increased immediately after the institution of ECLS; however, both ECF and TBW decreased during the bypass run, and post-ECLS levels of ECF and TBW were similar to those found prior to ECLS.(ABSTRACT TRUNCATED AT 250 WORDS)