Recombinant human growth hormone (rhGH) previously has been demonstrated to promote human or mouse T-cell engraftment in immunodeficient mice. We then wanted to examine long-term effects of rhGH on human cell engraftment in these mice. Mice with severe combined immune deficiency (SCID) were given human peripheral blood lymphocytes or human bone marrow cells and daily injections of rhGH (20 micrograms ip every other day). Upon later assessment for engraftment by flow cytometric analysis, it was determined that rhGH strongly promoted human T-cell engraftment in the thymus and spleens of these mice. However, there was considerable variability in both the incidence and extent of engraftment which appears to be due to donor-to-donor variation. Additionally, rhGH promoted B lymphomagenesis in these mice since long-term treatment of these xenogeneic chimeras with rhGH resulted in the increased incidence of human Epstein-Barr virus (EBV)-infected B-cell lymphoma. Thus, while rhGH can be used to optimize human T-cell engraftment in SCID mice, it also increases the likelihood of B-cell lymphoma generation when the donor is EBV infected. The results suggest that the activation of human T cells by rhGH results in an increased ability of these cells to traffic to the peripheral lymphoid organs of the SCID mice and results in a lymphoid microenvironment conducive to the outgrowth of EBV-transformed B lymphocytes.