Construction of mouse adenovirus type 1 (MAV-1) mutants is facilitating studies of adenoviral pathogenesis in the natural host. We have isolated the first site-directed viral mutants of MAV-1, and we are comparing effects of wild-type (wt) and these mutant viruses in infections of mice (Smith et al., submitted; Ying et al., submitted; refs. 1 and 2 ). The mutants have lesions in viral genes early region 1 (E1) or 3 (E3), and have altered lethality in adult mice.