The antibody to hepatitis B core antigen (anti-HBc) is belived to be a marker for natural infection with hepatitis B virus (HBV). In order to study the etiological role of HBV in relation to primary hepatocellular carcinoma (PHC), the anti-HBc in sera of 31 PHC patients was surveyed by the immune adherence hemagglutination method which was about 10 times more sensitive than the complement fixation method. Twenty two out of 31 PHC cases were positive for anti-HBc (71.0%). The is a higher rate of incidence than that of HBs-Ag (51.6%). However, high anti-HBc titer above 2(10) which might reflect current infection with HBV was observed in 15 of these 22 cases. The remaining 7 cases had a titer lower than 2(8); 5 of these patients had neither HBs-Ag nor anti-HBs in their sera. As control, 37 anti-HBs positive blood donors with no definite liver disease were surveyed for anti-HBc titer. Thirty-four of them were positive, but in the majority of cases, the serum titer was less than 2(9), which might only reflect previous infection with HBV. These findings indicate that not only the prevalence of anti-HBc, but also the determination of its real titer is quite important for studying the relationship of HBV to PHC.