A number of previous investigations in obese and normal-weight adults suggested a link between (usually) lower than normal erythrocyte Na+-K+ ATPase activity and obesity, although more recent studies have disputed this link. Developmental patterns of ATPase activity in children have not been studied. Infants of diabetic mothers show an increased incidence of macrosomia and such infants are at risk for later development of obesity. These children provide an ideal group to study the link (if any) between this enzyme and obesity, as well as changes in the level of the enzyme which may occur with age and/or the onset of obesity. The Na+-K+ ATPase levels in erythrocytes from 87 normal children and 27 infants of diabetic mothers were therefore studied by an ouabain-binding method. The study populations contained representatives of three ethnic groups (black, Caucasian and Hispanic) and individuals of normal body weight, as well as overweight and obese individuals. The ATPase activities were not correlated with body weight, sex, or age, nor was umbilical cord red cell ATPase correlated with birthweight. Several children who are being followed have shown considerable variation in percentage ideal body weight (IBW); however their ATPase levels have remained unchanged. There were, however, significant differences among the ethnic groups, with Caucasians having the highest values (0.443 +/- 0.012 pmol ouabain bound/10(9) cells). These data demonstrate the importance of matching study groups by race when investigating factors affecting this enzyme. The differences among the ethnic groups suggest a genetic component in the determination of the activity of this enzyme. This link was further investigated in 14 families and revealed considerable heterogeneity within a given ethnic group, with family members generally having similar enzyme activities, thus supporting a genetic basis for the different enzyme levels. Thus erythrocyte Na+-K+ ATPase in childhood is primarily regulated by genetic factors which are generally independent of body weight.