We have established a murine in utero bone marrow transplantation model system and have investigated the effects of donor strain differences, cell dose, and the number of injections on murine fetal survival and engraftment rates. In a series of experiments, 1221 nonanemic C57BL/6 fetuses were injected transplacentally on day 11 of gestation with 10 non-T-depleted adult bone marrow cells (BMC) from C57BL/6-CAST (congenic), BALB/c and DBA/1 (allogeneic) strains without recipient conditioning. Overall fetal survival was 45%, with a 4% engraftment rate in 475 evaluable day 5 newborns. Engrafted newborns initially had up to 75–100% donor peripheral blood cell engraftment, particularly with DBA/1 BMC. Surprisingly, a significantly (P< 0.05) higher incidence of engraftment was observed using allogeneic (5.2%) as compared with congenic donors (0.7%). However, engraftment in all groups was transient since engrafted recipients studied= 6 weeks post-natally had nondetectable levels of donor cells. In contrast, engraftment of congeneic marrow into anemic, stem cell–defective W"/" W" recipients lead to a higher incidence (4O%) of engraftment that persisted for= 6 weeks, increasing in the level of engraftment over time. Additional studies were performed in an attempt to further increase the incidence and permanence of engraftment. Neither doubling the cell dose nor doubling the number of injections improved engraftment rates in re-