The endometrium is a dynamic tissue that responds to hormonal cues and growth factors to accommodate, regulate, and nurture developing embryos. To provide clues about the molecular mechanisms underlying the responsiveness of this tissue, we have begun to identify genes that are expressed at specific stages of early pregnancy. One such gene, apolipoprotein J (apoJ), encodes a secretory glycoprotein capable of binding lipids and membrane-active proteins. Uterine apoJ gene activity was not detected immediately following fertilization, but glandular epithelial expression of apoJ mRNA appeared just before the time of blastocyst implantation and persisted postimplantation. During implantation, uterine luminal epithelial cells also expressed apoJ, but expression was excluded from luminal cells adjacent to the sites of attached blastocysts. ApoJ protein accumulated in the glandular and uterine lumens in proximity to the epithelial cells that expressed apoJ mRNA. We suggest that apoJ expression is a marker of uterine receptivity to blastocyst implantation. Subsequent expression of apoJ message in uterine stromal cell types and in circular muscle myocytes coincided with the onset of decidualization. During this period the myocytes of the longitudinal muscle layer showed no evidence of apoJ mRNA. ApoJ protein was localized to nondecidualized tissue but was not evident in decidualized cells. In contrast, the protein was dispersed throughout both the circular and longitudinal myometrium. In the uteri of hormone-treated females stimulated with oil, apoJ was also expressed during decidualization in stromal cells and in circular myocytes, indicating that signals specifically transmitted from the embryo itself are not responsible for apoJ mRNA accumulation.