The period of maximal endometrial sensitivity in the rat was characterized by high alkaline phosphatase activity in uterine luminal and glandular epithelium and endometrial stroma. The activity in endometrial stroma increased following decidualization. Pinopod development on the endometrial surface was first observed during the presensitivity period. Their number increased, apparently more so on the antimesometrial rather than the mesometrial segment of the uterus, on the day of maximal sensitivity. Inhibition in endometrial sensitivity by single anti-implantation (1.25 mg/kg, po) dose of centchroman on day 1 post-coitum (p.c.), although it did not affect alkaline phosphatase activity on days 2 and 3 p.c., caused complete inhibition in its activity in uterine luminal and glandular epithelium and pinopod development on days 4 and 5-coinciding, respectively, with time of entry of preimplantation embryos into the uterus and period of maximal endometrial sensitivity in this species. Significant decrease in enzyme activity was also evident in the entire endometrial stroma and myometrium, except blood capillaries, on these days. In comparison, prevention of entry of native embryos into the uterus by placing a ligature at the utero-tubal junction had no effect on pinopod development, but caused marked decrease in enzyme activity in luminal and glandular epithelium only during the immediate postimplantation period. The uterine lumen on the day of maximal sensitivity in centchroman-treated rats appeared highly distended and was lined with tall columnar epithelium, in comparison to low cuboidal epithelium in controls. The findings demonstrate: (a) a correlation between uterine luminal epithelial alkaline phosphatase activity and endometrial sensitivity; (b) complete inhibition in enzyme activity in luminal and glandular epithelium following centchroman treatment might be related to altered permeability characteristics of epithelial cells, which together with the absence of pinopods and highly distended uterine lumen on the day of maximal sensitivity, suggest inhibition of endocytosis/pinocytosis of luminal fluid, luminal closure, apposition of blastocyst trophoblast to luminal epithelium, and secretory activity of glandular epithelium; (c) pinopod development on the endometrial surface was independent of presence of viable blastocysts in utero; and (d) complete absence of pinopods suggests lack of endometrial sensitivity, but their presence might not necessarily indicate a sensitized endometrium in the rat.