Adenovirus internalization generally has been accepted to involve an interaction of the adenoviral penton base protein with alpha v beta 3 and alpha v beta 5 fell surface integrins, In this study we show that exposure of a panel of melanoma cells to the beta 1-activating antibody TS2/16 rendered such cells more susceptible to adenovirus infection, This increase In adenoviral infectivity paralleled effects on cell adhesion, and both these characteristics Here mediated, in part, by the alpha 5 beta 1 integrin. These observations suggest that alpha 5 beta 1 may act as an alternative adenovirus receptor and that integrin-activating strategies may improve the efficacy of recombinant adenoviruses as vectors for gene therapy.