Activity of glucose-6-phosphate dehydrogenase (G6PD), which has a gene locus on the X chromosome, and sex chromatin (SC) frequencies were measured during pregnancy and lactation. This was done to determine the response of this genetic-enzymic system to these periods of physiological stress. Dynamic changes in liver, ovarian, and adrenal G6PD activity were seen during pregnancy and lactation. Markedly depressed liver G6PD activity was seen on Day 1 of pregnancy and in reproductively senile animals. Liver G6PD activity increased (p < .01) from Day 1 through Day 20 of pregnancy and again from parturition until the day of weaning when enzyme activity was significantly higher (p < .01) than that of all other groups examined. Ovarian G6PD activity decreased to Day 8 of pregnancy, and then increased until parturition at which time enzyme activity was higher (p < .01) than that of all other groups. From parturition to Day 15 of lactation, ovarian G6PD activity decreased significantly, but returned to estrus values at weaning. Extremely how ovarian G6PD activity was seen in reproductively senile animals. Adrenal G6PD activity was depressed below estrus values during pregnancy and was elevated during lactation. Few significant changes were seen in kidney and neural tissues. Dynamic changes in liver and kidney SC frequencies were also seen during pregnancy and lactation, suggesting that the X chromosome responds to changing cellular environments. An inverse relationship between G6PD activity and SC frequencies, which might be expected, was not observed except in reproductively senile animals.