Patients affected with AIDS develop a wide range of cutaneous neoplastic and nonneoplastic disorders. However, it is not clear whether pathological skin changes, observed in HIV-1 seropositive subjects during the course of disease are correlated to HIV-1 infection. To verify the effect of HIV-1 on human epidermal keratinocytes (HEKs), we performed virological and ultrastructural (transmission and scanning electron microscopy - TEM, SEM) studies. For this purpose cultured HEKs were studied following incubation with cell-free HIV-1 or HIV-1/infected cells, treatment with recombinant gp120 and treatment with Tat protein. PCR analysis performed on cell-free, virus-treated HEKs, constantly demonstrated negative results. Ultrastructural observations showed cytotoxic, stress-induced HEK changes, including : 1. cell vacuolization ; 2. disordered cytoskeletal arrangement ; 3. junctional leakage ; 4. surface blebbing. Our results suggest that, although HEKs appear resistant to HIV-I infection in our experimental setting, they undergo a cascade of stress-induced subcellular events which possibly impair their in vivo physiological functions.