Xenogeneic mouse models are widely used for the study of human tumor growth and metastasis. To date, few methods have been developed to track and quantitate the colonization of mouse organs with transplanted human cells. In this paper, a family of nonradioisotopic DNA oligonucleotide probes that are complementary to sequences within the human Alu element are characterized. These probes can be used in Southern hybridization reactions to quantitate the colonization of mouse organs with human derived cells. One oligonucleotide probe, the Alu-C probe, was identified as the most sensitive and specific in the family of probes synthesized for the distinction of human genomic DNA in a mouse genomic DNA background. The Alu-C probe can identify 0.05 ng human diploid DNA in a mouse background of 500 ng of genomic DNA. This represents 7.5 human diploid cells admixed with 75,000 mouse diploid cells. The Alu-C probe can therefore be employed to assess human colonization in xenograft models for a variety of human tumors and non-neoplastic tissues.