The effects of HIV infection on HBV and HDV replication and liver damage were evaluated by comparing the findings from 48 anti-HIV-positive HBsAg chronic carriers with those from 22 matched anti-HIV-negative subjects. The state of HBV/HDV infection was also related to the degree of immunodeficiency of the anti-HIV-positive patients. Most patients were intravenous drug addicts (IVDA) (84.2%); male homosexuals represented only a small proportion (7.1%). Serum HBV-DNA was detected more frequently in anti-HIV-negative than in anti-HIV-positive patients (50% vs. 35%) despite evidence of HDV replication in the anti-HIV-negative group (P = 0.02). Seroconversion from ongoing to inactive HBV infection occurred in 45% of anti-HIV-negative patients as well as in 23% of anti-HIV-positive patients (P = ns). The difference in severity of liver damage between the two groups was not statistically significant (P = 0.84). Furthermore, in the anti-HIV-positive subjects, HBV and/or HDV activity was detected in 63% of patients with mild immunodeficiency (CDC groups II and III with a total CD4 count greater than 400/mm3) and also in 75% of ARC-AIDS patients (CDC groups IV A-IV C) (P = ns). Severe hepatic disease occurred in subjects with CD4 counts above or below 400/mm3 (13 vs. 6, respectively). In conclusion, the data do not demonstrate that HBV or HDV infections are modified by HIV. The epidemiological background of the patients investigated and the extensive spread of hepatitis viruses in Italy before the appearance of HIV may account for the lack of relationship between HIV and HBV/HDV infections.