SUMMARY: Carbonic anhydrase was shown to occur in the female reproductive tract of a variety of mammalian species. The uterine endometrium, placental tissue and the Fallopian tubes were established as the main loci of carbonic anhydrase activity. The enzyme was present in the endometrium of the non-pregnant rabbit in a low concentration. Following mating no perceptible increase in enzyme content occurred before the 4th day; from then onwards the activity continued to rise, reaching a maximum by about the 8th day; with advancing foetal development the endometrial activity declined, but at the same time the enzyme could be demonstrated in the placenta, chiefly in the maternal, but to a small extent also in the foetal, part. The behaviour of carbonic anhydrase in the pseudopregnant uterus or in response to ovulating doses of gonadotrophin or copper salts, presented essentially the same picture as in the early phase of pregnancy; excessive doses of gonadotrophin were capable of increasing the enzyme content within 2 days of administration; moreover, their effect persisted for 20–24 days. Progesterone, and to a smaller extent ethisterone and methyltestosterone, injected into oestrous adult or into oestrogen-primed immature rabbits, produced marked increases in the content of uterine carbonic anhydrase, the extent of which depended upon the dose. Whereas the endometrium of rats, hamsters and guinea-pigs was completely devoid of carbonic anhydrase, both in pregnant and non-pregnant females, the placenta of these animals contained the enzyme, again mainly in the maternal portion. The uterine mucosa of the non-pregnant sheep was conspicuously rich in carbonic anhydrase, the activity being largely restricted to the intercotyledonary areas; the uterine portion of the Fallopian tubes was also remarkably active. In this species the uterine carbonic anhydrase was found to be independent of ovarian function: the enzyme was present in the uteri of prepubertal lambs, and it was fully preserved in ovariectomized animals. Considerable enzymic activity was found in the sheep placenta. No carbonic anhydrase was found in the uterus or Fallopian tubes of the non-pregnant pig; the pig placenta, however, was very active, the enzyme being located in the chorion in late pregnancy. In the non-pregnant cow only the fimbrial portion of the Fallopian tubes showed enzymic activity, especially marked in the immediate post-ovulatory phase. No carbonic anhydrase was present in the non-pregnant uteri or Fallopian tubes of mares, cats or dogs. By introducing parenterally large amounts of a sulphonamide inhibitor of carbonic anhydrase it was possible to inhibit the enzyme in vivo, both in the rat placenta and in the progestational rabbit endometrium.