A molecular clone of the AIDS-associated retrovirus (ARV-2) was transfected into human T lymphocyte and monocyte cell lines as well as mouse, mink, monkey, and human fibroblast lines. A replicating virus with cytopathic and biologic properties of ARV-2 was recovered from all the cell lines. The animal and human fibroblast cells are resistant to direct infection by ARV, and in these experiments virus production in the fibroblast lines, especially mouse, was reduced compared to human lymphocytes. However, human fibroblasts were more permissive to virus expression than mouse cells. These results show that, whereas the primary block to ARV infection in certain cells may occur at the cell surface, intracellular mechanisms can also participate in controlling virus replication. The results have relevance to vaccine development and encourage further work with modified molecular clones to examine regions of the ARV genome necessary for cytopathology and replication.