The course after hepatitis B virus infection seems to be determined by the host's immune response, which in turn may be regulated by the major histocompatibility complex. In order to find a possible relationship between the course of disease and the phenotype frequency of HLA determinants, we studied 396 Dutch subjects of northern European local race. Six groups of individuals with various courses after hepatitis B virus infection were compared to healthy controls. The hepatitis B patients were grouped according to standard criteria: 47 had recovered from acute symptomatic hepatitis B virus infection; 60 had recovered from asymptomatic hepatitis B virus infection; 26 were asymptomatic hepatitis B surface antigen carriers; 16 had chronic persistent hepatitis B; 37 had chronic active hepatitis B, and 10 had chronic active hepatitis after elimination of hepatitis B antigens. Twenty-nine Class I and 13 Class II HLA antigens were assayed by standard microlymphocytotoxicity tests. The phenotype frequency of the Class II antigen DQw1 appeared to be significantly lower in patients with chronic active hepatitis B virus infection. Some other HLA specificities showed deviations from control values, but they were not statistically significant after correction for the number of antigens tested. In conclusion, we have found no evidence that the elimination of hepatitis B virus is related to HLA phenotype. DQw1, however, may affect the morphologic type of chronic hepatitis B infection, since its presence may protect against chronic active hepatitis.