To investigate the clinical value of delta agent infection in HBsAg positive chronic hepatitis, we detected anti-delta antibody (anti-delta) in serum and delta antigen (delta-Ag) on sequential liver biopsies of nine patients with HBsAg-positive CPH and 45 patients with HBsAg-positive CAH without cirrhosis observed for at least 2 years. The initial group of patients with CAH was composed of 54 patients who were consecutively either left untreated or treated with 15 mg of prednisolone daily. Nine patients dropped out. Delta-Ag was searched by the direct immunofluorescence technique. HBsAg, anti-delta, HBeAg and anti-HBe were detected by RIA. All CPH patients were delta-Ag negative in the 1st liver biopsy and anti-delta negative in serum. Out of these nine patients, seven remained delta-Ag negative CPH throughout the observation and the remaining two became delta-Ag positive, anti-delta positive and developed CAH. The 73% of patients with CAH were delta-Ag positive on the 1st biopsy and anti-delta positive in serum. The patients in the delta-Ag positive group (24 were always delta-Ag positive and two became delta-Ag positive during the observation) more frequently than those in the delta-Ag negative group (10 were always delta-Ag negative and nine became delta-Ag negative during the study) showed deterioration or died (77 vs. 16%; P less than 0.001). Neither in the delta-Ag positive group nor in the delta-Ag negative group did prednisolone modify the course of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)