ABSTRACT— In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD–Ag) in the liver tissue was the criterion used to identify HDV infection. HD–Ag was observed in none of the 7 patients with non-specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD–Ag negative patients in this study, the 64 HD–Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p < 0.01) and less frequently CPH (10.9 vs. 29.5%, p < 0.01). Of the 139 HD–Ag negative patients, 80 were anti-HD positive and 59 anti-HD negative. The 59 patients with no HD–Ag or anti-HD showed severe CAH less frequently than the 64 HD–Ag positive patients (6.8 vs. 29.7, p < 0.01) and CPH more frequently (44.1 vs. 10.9, p < 0.001). Both in CPH and CLH the presence of HD–Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD–Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p < 0.05). Patients with HD–Ag positive cirrhosis were younger than the HD–Ag negative patients (p < 0.05). The data suggest that HDV replication is responsible for a more extended necrosis or degeneration of the hepatocytes and for a more active disease in CPH, CLH and CAH. These Findings per se seem to indicate an unfavourable course of the disease due to HDV infection.