The ability of herpes simplex virus 1 to replicate in cells transformed by adenovirus type 5 is strongly dependent on the origin of the cells. Studies show that adenovirus transformed rat cells lose their permissiveness while cells of hamster or human origin retain their ability to replicate HSV although at a reduced level when compared to the untransformed parent cells. One line of adenovirus transformed rat cells, 107, demonstrates thermosensitive events, allowing HSV to replicate at 34 degrees C but not at 37 degrees C. Analysis of the biochemical events taking place at 37 degrees C showed that virus-specific DNA synthesis was greatly reduced but that all of the late virus structural proteins could be observed after SDS-polyacrylamide gel electrophoresis. It was also demonstrated that shut-off of host macromolecular synthesis appeared to be less efficient after HSV infection of 107 cells than after infection of more permissive cells such as the non-transformed REF line. Collectively the data show that interactions between HSV and the host cell are perturbed when the cell is transformed by type 5 adenovirus. The degree of perturbation ranges from a slight reduction in number of progeny to a completely abortive infection.