SCID and RAG-2 deficient mice were transplanted intraperitoneally with human peripheral blood lymphocytes (hu-PBL-SCID and hu-PBL-RAG mice). Seven days after transplantation the mice were immunized with a pneumococcal polysaccharide vaccine. Flow cytometry analysis of cells from the peritoneal cavity and the spleen after 8-10 weeks revealed that human cells had more limited engraftment in RAG than in SCID recipient mice, and that more human cells were found in the spleen than in the peritoneal cavity. Functionality of the human cells recovered from these two locations was explored by the counting of human immunoglobulin secreting cells (hu-ISC). A total of 83% of the hu-PBL-SCID mice and 29% of the hu-PBL-RAG mice had detectable hu-ISC in the peritoneal cavity and/or the spleen. The kinetic profiles of human immunoglobulins in the mouse sera during the experiment showed donor dependency. More than 90% of the hu-PBL-SCID mice had detectable levels of human IgG, IgM and IgA, while 78% had detectable levels of IgE, whereas detectable levels of IgG, IgM, IgA and IgE were measured in 37%, 64%, 68% and 23% of the hu-PBL-RAG mice, respectively. Forty-seven per cent of immunized hu-PBL-SCID mice showed a human antipneumococcal IgG level that was significantly above the background level in non-immunized mice, while none of the hu-PBL-RAG mice produced any detectable levels of human antipneumococcal IgG. In short, human PBL showed a better engraftment and a better antibody response when transplanted into SCID mice than into RAG mice.