Simultaneous presence of hepatitis B surface antigen (HBsAg) and antibodies to the surface antigen (anti-HBs) was detected in 32 out of 89 Dutch chronic hepatitis patients of Caucasian race. HBsAg was subtyped ad in 28 and ay in four cases. Anti-HBs could be subtyped in 25 cases using reference antigens discriminating between d, y, and w1-4 subdeterminants. In 20 patients HBsAg subtype ad (HBsAg/ ad) was accompanied by antibody to subdeterminant y (anti-y), whereas HBsAg/ ay and anti-d were simultaneously detected in the serum of one patient. The antibody pattern in sera from the remaining patients was complex. Eighteen anti-HBs-positive patients were matched for age, histology, and hepatitis B e antigen (HBeAg) status with 18 anti-HBs-negative patients. Differences in risk factors for acquiring a hepatitis B infection were not found. These results do not support the hypothesis that co-occurrence of HBsAg and anti-HBs is due to two consecutive infections with hepatitis B virus. The frequency of the co-occurrence of HBsAg and anti-HBs was found to be related to the degree of progressive liver disease, since anti-HBs was found in three out of 23 asymptomatic carriers, in four out of 20 chronic persistent hepatitis patients, in 20 out of 41 chronic active hepatitis patients, and in all five patients with chronic active hepatitis and cirrhosis. The high frequency of anti-HBs in advanced liver disease may be the result of a disturbed immunologic response mechanism.