The mammary gland tissue hexose monophosphate dehydrogenase activities were low in virgin, pregnant and weaned rats, but increased at the onset of lactation. The muscle and liver giucose 6-phosphate dehydrogenase activity peaked atearly and late lactation respectively. The liver 6-phosphogiuconate dehydrogenase peaked in late pregnancy and remained elevated through lactation. The muscle 6-phosphogiuconate dehydrogenase peaked at the onset of lactation. The adipose tissue hexose monophosphate dehydrogenases exhibited small changes during pregnancy and lactation. The spleen hexose monophosphate dehydrogenases did not respond to lactation An overshoot in both the liver and the adipose tissue hexose monophosphate dehydrogenases was observed on weaning. Serum glucose levels remained unchanged throughout pregnancy, lactation and weaning. Only liver glucose 6-phosphate dehydrogenase activity correlated with plasma insulin, which also correlatedpositively with food consumption. The results demonstrate that tissue-specific control of the hexose monophosphate dehydrogenases occurs in the female rat during its complete lactation cycle.