Mouse epididymal sperm cells have the spontaneous ability to take up exogenous DNA. A proportion of the sperm-bound DNA is further internalized into sperm nuclei. In this work, we have followed up the fate of the foreign DNA upon internalization into nuclei. We have found that the internalized plasmid DNA becomes tightly associated with the nuclear scaffold, is extensively rearranged, and undergoes recombination with the sperm genomic DNA. Sequence analysis of two randomly selected clones independently recovered by plasmid rescue from pSV2CAT plasmid-challenged sperm cells shows that DNA fragments from the plasmid are integrated into the mouse sperm genome. The sites of integration are identical in both clones, suggesting that these events do not occur randomly, but take place at preferential sites. A topoisomerase II consensus sequence is found adjacent to one end of the integration site, suggesting a possible role of this enzyme in the process of nonhomologous recombination.