The design of effective immune therapies to eradicate residual malignant cells following chemotherapy is dependent upon understanding immune and hematopoietic dysfunctions present in this period. Toward this end, we have examined three facets of post-therapy cellular function. First, we have determined through preclinical animal models and clinical studies that the majority of CD4 T cells present in the post-chemotherapy period are of memory phenotype, and are derived from mature peripheral T cells. The origin of T cell populations, whether from residual mature T cells, or from newly generated naive cells from the thymus, is relevant to T cell competence and responsiveness to malignant cells. The second set of studies concerns the in vitro generation and in vivo maintenance of T lymphocyte populations which may mediate anti-tumor effects. Culture conditions were established for bulk generation of functionally distinct alloreactive (donor anti-host) murine CD4+ ("Th1/Th2") and CD8+ ("Tc1/Tc2") T cell subsets. Donor CD4+ T cells of Th1-type mediated both lethal GVHD and GVL. In contrast, in vitro generated donor anti-host CD8+ cytotoxic T cells secreting either Type l ("Tc1 subset") or Type II ("Tc2 subset") cytokines were found to mediate potent GVL effects with reduced GVHD. The third facet of the work concerns characterizing quantitative and functional alterations in hematopoietic cell populations following chemotherapy. It Was found that chemotherapy damage to primitive hematopoietic progenitors occurred even though the number of committed progenitors and CD34+ cells had recovered under the influence of hematopoietic cytokine therapy. Such treatment did not therefore protect the primitive progenitor pool from toxic effects of chemotherapy. These results have implications for T cell regeneration via the thymic pathway and for gene manipulation of hematopoietic stem cells in patients receiving chemotherapy for cancer.