Severe combined immunodeficient (SCID) mice accept human xenografts and can act as a model for human immune functions. Murine natural killer cells (NK), however, represent an important barrier for the reconstitution of SCID mice with human peripheral blood leukocytes (Hu‐PBL). We investigated the effect on Hu‐PBL survival of pretreatment with TM‐β1, a rat monoclonal antibody for the mouse IL‐2 receptor beta chain. TM‐β1 greatly improved the survival of Hu‐PBL. Human lymphocytes, predominantly T cells, survived in the peritoneum and infiltrated spleen and lungs already 1 week after engraftment and liver and thymus from 2 weeks on. Secondary humoral responses were evaluated with Hu‐PBL from a donor immune to hepatitis‐B surface Ag (HBsAg) and tetanus toxoid (TT). TM‐β1 pretreatment enhanced the recall Ig response to HBsAg and did not affect the baseline anti‐TT Ig production. In conclusion, TM‐β1 pretreatment of SCID mice significantly improves the survival and functionality of the Hu‐PBL graft.