Among the goals of an optimal gene transfer system are a predictably high efficiency of transfer and the ability to confer stable gene expression. An additional benefit of strategies designed to target tumor or effector cells could be the induction of a bystander effect. Although tumor killing by the bystander effect in vivo has been obtained in several types of malignant tumors, it has not been reported for T lymphomas. The goals of this work were to determine the stability of the expression of the herpes simplex virus type-1 thymidine kinase and the low-affinity receptor for nerve growth factor truncated of its intracellular domain (deltaLNGFR) genes inserted in a murine T lymphoma; in addition, we sought to determine whether a bystander effect (direct or indirect) was present after treatment of the transduced tumor with ganciclovir. This study demonstrates a high level of stable expression of both genes in the T lymphoma in vitro and in vivo. However, we could not detect direct or indirect bystander effects in vivo mediated by the herpes simplex virus thymidine kinase/ganciclovir system in this tumor of lymphocyte origin. This is the first report to investigate bystander effects in vivo on a T-cell lineage tumor; in addition, this report has implications for the therapeutic transfer of non-transformed, antigen-specific T cells in vivo.