 The pathogenesis of the initial infection at the level of the foreskin involves tissue macrophages, cell receptors and a moist, poorly keratinized inner prepuce. The first cellular target of the HIV virion on the human genitalia are the tissue dendritic cells in the lamina propria of the submucosa14. These cells express surface CD4 receptors and CCR5 co-receptors for which HIV has high affinity. In intact human skin, the dendritic cells are shielded from the outer environment by the relatively thick layer of keratin covering the surface of the epithelia. Tissue studies of the human foreskin have shown that the inner lining of the prepuce, exposed during a penile erection, has a thin keratin layer that is very susceptible to microscopic abrasions and can expose the tissue macrophages making them vulnerable to infection by HIV15. 