The growth properties of human T-cell leukemia virus Tax1-transduced primary human T cells derived from peripheral blood lymphocytes were compared with those of the same subset of T cells transduced with a control vector. Tax1-transduced T cells exhibited slightly elevated responsiveness to externally added interleukin-2 (IL-2) and a markedly higher proliferative response to stimulation with anti-CD3 antibody. The proliferation after anti-CD3 antibody stimulation was mainly via an IL-2-independent pathway. Therefore, some other mechanism than the previously proposed IL-2 autocrine model seems to be involved in the process of deregulation of T-cell proliferation by Tax1. Moreover, Tax1-transduced T cells have continued to proliferate in medium containing IL-2 long after control T cells ceased to grow, and so they are considered to be immortalized.