A histochemical investigation of enzyme activities in the uterine endometrium of mice from Days 4 to 8 of the first pregnancy is described, Day 1 being the day on which a copulation plug appeared in the vagina. The timing and cellular location of changes in reactions for lactic dehydrogenase (LDH) are compared with those for 5′-nucleotidase (AMPase), α-glucan phosphorylase, nicotinamide adenine dinucleotide (NAD) -diaphorase, succinic dehydrogenase (SDH ), adenosine triphosphatase (ATPase) and alkaline phosphatase (APase), and of glycogen and lipids. The appearance of APase, deposition of glycogen and changes in LDH or phosphorylase in the antimesometrial stromal cells at future implantation sites were preceded by the disappearance of AMPase from these cells before implantation on Day 5. This, in turn, may retard the dephosphorylation of adenosine-5′-monophosphate and make more of this substance available for activation of phosphorylase in these cells. Increased reactions for LDH first appeared early on Day 5 (before implantation) in the cells of the APase-free primary decidua. These were accompanied by increased reactions for SDH but preceded the first appearance of glycogen in the same cells. Later on Day 5 and throughout Day 6, there was further strengthening and spread of increased LDH activity accompanied in the same cells by increased phosphorylase, reappearance of strong AMPase, increased SDH, and by deposition of glycogen. The patterns of the rise and fall of glycogen in the decidua and of the accompanying changes in enzyme activities on these days support the concept of a metabolically active tissue with a high rate of glycogen turnover. The disappearance of glycogen from the cells of the antimesometrial decidua on Day 7, with continued increase in LDH, phosphorylase and AMPase, suggest that glycolysis is in the ascendant here, while the accompanying accumulation of glycogen in the `glycogen wings' and peripheral stroma, without marked increase in LDH, indicates that this is an area of glycogen storage. The use of urea and pyruvate to inhibit, respectively, the M- and H-type subunits of LDH showed a great predominance of Msubunits throughout the endometrium. This would enable the tissue to derive energy from anaerobic pathways when oxygen is deficient. Distribution and changes in NAD-diaphorase paralleled those of LDH, and changes in SDH also showed some parallel. There was a reciprocal relationship between distribution of LDH and that of lipids in the decidual cells. The timing of the disappearance of ATPase and periodic acid-Schiff reactivity from endometrial capillaries was compared with that of the other changes and the implications are discussed, particularly in relation to recent reports of variations in uterine oxygen tension in the rat during the same period. No demonstrable changes were observed in the endometrium between decidua.