Growing interest in adenoviral gene-transfer vectors, stimulated by efforts to develop in vivo gene therapy for cystic fibrosis, has led to an evaluation of their use in many other applications of in vivo gene therapy. Studies are beginning to define strategies for the efficient, albeit transient, expression of the transferred gene and have further identified and partially characterized important host responses to in vivo gene transfer that modulate the duration of expression of the transgene. Ongoing work is actively exploring these issues, with a view to the design of the next generation of adenoviral vectors.