Developmental changes in Na+/K(+)-ATPase enzyme activity have been documented postnatally in a number of organs, but little is known about prenatal levels or the factors affecting them. This study determined the normal developmental patterns of Na+/K(+)-ATPase activity in the pancreas, liver, small intestine, kidneys, and colon of pre- and postnatal rats. In addition the effect of betamethasone administration on enzyme activity was determined both antenatally and postnatally. The individual organs showed a variable pattern of maturational change in enzyme activity. In the pancreas, changes in Na+/K(+)-ATPase activity appeared to reflect the changing ratio of ductular to acinar cells. The pattern of enzyme activity in the small intestine was similar to that of the kidney and was inversely related to that of the colon. Enzyme induction by administration of betamethasone was also variable and bore no relationship to the DNA/protein ratio. In the preterm rat, betamethasone increased the Na+/K(+)-ATPase activity only in the colon. Use of steroids to increase enzyme activity in the colon at an early stage of development may have therapeutic implications for treating abnormalities of potassium and sodium homeostasis in the preterm infant.