Sexual transmission of HIV is one of the main routes of transmission of AIDS. Despite the fact that the virus has been found in the semen and germ cells of patients with HIV, little is known about how the virus infects the cells of the genital tract. We studied the cellular distribution of CD4, a receptor necessary for HIV infection, and the major HIV co-receptors CCR3, CCR5 and CXCR4 in the rat and human testis. We used RT-PCR, Northern blotting and immunohistochemistry to demonstrate that CCR3 is absent from the testes of both species, whereas CCR5 and CXCR4 are present on the resident testicular macrophages in the interstitial space but not in the germ cell line. All of the human testicular macrophages expressed the markers CD45 and MAC387 and most also expressed CD4. Thus, our data suggest that macrophages in the testis may be infected by HIV and that these macrophages may be a site of early viral localization and a potential HIV reservoir. This may in turn alter the activity of Leydig cells and subsequently affect spermatogenesis.