The epidemiological, clinical and therapeutic features of HIV disease diagnosed in 41 immigrants from outside of the European Union (EU), were compared with those of 123 Italian and EU patients, in a cross-sectional case-control study, with individuals matched according to age and gender. In total 4·15% of our patients came from outside of the EU (51·2% of them from subsaharan Africa), with a proportional predominance of females, and heterosexual and perinatal transmission of HIV disease (P < 0·0001 and P < 0·02, respectively). Compared with Italian and EU subjects, patients coming from abroad had a shorter duration of known HIV infection (P < 0·001), but only some subjects were aware of their HIV disease prior to immigration, or acquired HIV infection only after coming to Italy (14·6% and 12·2%, respectively). No cases of HIV-2 infection or co-infection were detected in either study group. Compared with controls, patients coming from outside of the EU had a comparable clinical and immunological status, and had similar antiretroviral therapy, which was administered earlier (P < 0·0001), and proved better tolerated (P < 0·04), than in Italian and EU subjects. The apparently more limited virological response (as expressed by a higher mean plasma viral load, and a lower rate of viral suppression at the last visit; P < 0·001 and P < 0·05, respectively), was probably a bias due to the shorter mean overall follow-up time (P < 0·0001), and the shorter mean duration of antiretroviral treatment (11·1±2·2 months of immigrants vs. 16·2±6·7 months of controls; P < 0·0001).