Serological markers of hepatitis delta virus (HDV) infection were found in 18 (12%) of 146 consecutive patients with chronic hepatitis B, and the characteristics of patients who had antibody to HDV (anti-HDV-positive) were analyzed. During one to 15 years of follow-up, histological deterioration was documented in 77% of anti-HDV-positive patients; however, in hepatitis B surface antigen (HBsAg) carriers without HDV infection, histology deteriorated in 30% but improved or remained unchanged in the majority of patients (P less than .01). In seven (70%) of the 10 anti-HDV-positive patients who showed transition from chronic active hepatitis to cirrhosis, this event was observed within the first two years of follow-up. The probability of evolution to cirrhosis was significantly higher in anti-HDV-positive patients than in patients without antibody to HDV (P less than .001). These findings indicate that HDV infection in patients with chronic hepatitis B is associated with a more-rapid progression to cirrhosis compared with HBsAg carriers with chronic hepatitis and no evidence of HDV infection.