The ability to reconstitute RAG-1 deficient (R-) mice with human perip
heral blood cells was examined using four different host preparative r
egimens. Our results indicate that while untreated R-mice could be rec
onstituted with human cells, pre-conditioning with either 5Gy whole bo
dy irradiation (WBI) or anti-asialo GM1 rabbit anti-serum led to an in
crease in the frequency of CD45(+) human cells that could be detected
in the circulation. Pre-conditioning with both anti-asialo GM1; and WB
I led to a further increase in the frequency of circulating human cell
s in reconstituted R- mice. Human CD45(+) cells were detected in the s
pleen and lymph nodes, but not the thymus of reconstituted mice pre-co
nditioned with WBI and anti-asialo GM1. Our results suggest that mouse
NK cells and a limitation in physical space are limiting factors medi
ating resistance to human cell engraftment in R- mice.