A retrospective analysis of 135 drug addicts followed between 1986 to 1987, was done, in order to asses the seroprevalence of hepatitis B virus (HBV), hepatitis Delta virus (HDV), hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV), as also their clinical and prognostic significance. A high prevalence of HBV, HDV and HCV infection was observed in this study: 81%, 64% and 83% respectively; in contrast just one case was positive for HIV. Among the drug addicts the frequency of multiple infections (HBV/HCV 51.6%; HBV/HDV/HCV 18.7%; HBV/HDV 2.2%; HCV/HIV 1.1%) was highest in comparison with isolated (HBV 5.5%; HCV 12.1%) or absent infection (73.6% vs 17.6% vs 8.8% respectively; p less than 0.001). Eleven of 12 (92%) patients with Delta hepatitis and HCV superinfection were seronegative for IgM anti-HD; in contrast the case without HCV superinfection was IgM anti-HD positive. In the former group the Alanine Amino-transferases (ALT) were significantly lower comparatively with those HBV positive patients superinfected by HCV (97 +/- 92 IU/L vs 249 +/- 125 IU/L; p = 0.001), and were not different from drug addicts with isolated HCV infection (62 +/- 49 IU/L). The results of this study indicate, a low prevalence of HIV infection in the Portuguese drug addicts and a high frequency of multiple HBV, HDV and HCV infection in the same period of study. Our observations suggest that HCV may have the capacity to inhibit the replication and pathogenic activity of hepatitis Delta virus.