Human immunodeficiency virus type 2 (HIV-2) infection is endemic in West Africa, where it is responsible for many cases of AIDS. HIV-2-infected subjects have been described in other countries, mainly African immigrants, although infection in native individuals has been reported as well. The first cases of HIV-2 infection in Spain were identified in 1988. Through December 1995, 56 HIV-2 infected individuals have been diagnosed, primarily in large urban areas (23 cases in Madrid and 18 in Barcelona). All are African immigrants, except for 12 natives (21.4%), six of whom acquired the infection in endemic areas; the remaining six (2 women with numerous sexual partners and 4 homo/bisexual men) acquired the infection in Spain. Heterosexual transmission was probable in all but seven cases: five homo/bisexual males, a subject who likely acquired infection through parenteral exposure, and a child born to an HIV-2-infected mother. Nine patients (all Spanish born) have developed AIDS (16%), six of whom have died. In conclusion, HIV-2 infection is present in Spain at a low rate, and there is little evidence supporting an emerging ongoing transmission outside the population of African immigrants.