This study describes an in utero approach for overexpressing genes in a cell-type directed manner. It uses an avian leukosis retroviral expression system coupled with a transgenic mouse line expressing the viral receptor tv-a from a tissue-specific promoter (RCAS-TVA system) (Federspiel et al., 1994, and reviewed in Fisher et al., 1999). A transgenic mouse line was generated expressing tv-a from the Dopachrome tautomerase promoter (DCT-tv-a) in embryonic melanocyte precursors (melanoblasts). RCAS virus encoding beta-galactosidase (RCAS-LacZ) or tyrosinase (RCAS-Tyr) was injected in utero into embryonic day 12.5 albino (tyrosinase inactive) mouse embryos. Animals were analyzed for beta-galactosidase activity or tyrosinase activity (hair pigmentation). RCAS gene expression was detected in 44% and 25% of the transgenic mice, respectively. We demonstrate the RCAS-TVA system coupled with the DCT-tv-a line of mice can be used for in utero infection.