Estrus, gestation, and placentation were studied in the Virginia opossum (Didelphis virginiana) and the gray short-tailed oppossum (Monodelphis domestica), representatives of the prototypic, New World marsupial family Didelphidae. Didelphis is a large (3,000 g), pouched opossum that exhibits a 28-day estrous cycle, spontaneous estrus and ovulation, and a high ovulation rate (60 ova per cycle). Monodelphis is a small (100 g), pouchless opossum with male-induced estrus and ovulation and a moderate ovulation rate (12 ova per cycle). Implantation occurs on day 10 of the 13-day gestation period in Didelphis and on day 12 of the 15-day gestation in Monodelphis. Gestation and placentation, including the ultrastructural features of trophoblastic apposition to the uterine mucosa, are very similar in Didelphis and Monodelphis. Differences, such as a larger increase in uterine volume and a more highly folded endometrium following implantation in Monodelphis are minor. They appear to be related to the smaller maternal body size and the relatively larger uterine load of embryos in Monodelphis. Because body size is one of the major variables among New World marsupials, the descriptions of gestation and placentation presented here for Didelphis and Monodelphis, provide a basis for comparison in future studies of didelphid marsupials.