Adenoviral vectors, including mutant adenoviruses, that have restriction sites in the E3 region, that facilitate its partial or total deletion, or select genes contained therein, and optionally compositions and methods for substituting heterologous gene(s) in the partially or totally deleted E3 region(s), which heterologous gene(s) being operably linked to endogenous adenoviral transcriptional control sequences will exhibit an expression pattern, both in terms of timing and degree of expression, similar to the endogenous adenoviral gene(s) that it replaces, and further optionally including mutations in other parts of the adenoviral genome, including certain E1B or E1A regions, and that have applications for diagnosing or treating disease, preferably disease involving unwanted cell growth, including cancer.