The objective of this study was to determine whether stromal and/or epithelial relaxin receptor (LGR7) is required for relaxin to promote proliferation and inhibit apoptosis of stromal and epithelial cells in the mouse cervix and vagina. Tissue recombinants were prepared with stroma (S) and epithelium (E) from wild-type (wt) and LGR7 knockout (ko) mice: wt-S+wt-E, wt-S+ko-E, ko-S+wt-E and ko-S+ko-E. Tissue recombinants were grafted under the renal capsule of intact syngeneic female mice. Following 3 weeks of transplant growth, hosts were ovariectomized and fitted with silicon implants containing progesterone and estradiol-17 (designated day 1 of treatment). Animals were injected sc with relaxin or relaxin vehicle PBS at 6-h intervals from 0600 h on day 8 through 0600 h on day 10 of treatment. To evaluate cell proliferation, 5-bromo-2'-deoxyuridine (BrdU) was injected sc 10 h before cervices and vaginas were collected at 1000 h on day 10. TUNEL was used to quantify apoptosis. Relaxin markedly increased proliferation and decreased apoptosis of epithelial and stromal cells in tissue recombinants containing wt stroma (P < 0.01), but had no effect on tissue recombinants prepared with ko stroma, regardless of whether epithelium was derived from wt or ko mice. In conclusion, this study shows that LGR7-expressing cells in the stroma are both necessary and sufficient for relaxin to promote proliferation and inhibit apoptosis in both stromal and epithelial cells of cervix and vagina, while epithelial LGR7 does not effect these processes.