The occurrence of apparent false positive immunoperoxidase staining for hepatitis B surface antigen (HBsAg) led to the evaluation of several commercial antisera for usefulness in the diagnosis of hepatitis B by immunohistochemistry. One commercial antibody to hepatitis B core antigen (HBcAg) was tested and found to give sensitive and specific staining, with only a few false negatives and no false positives. Of three antibodies to HBsAg, one gave good staining results that were consistent with serologic data; one had many false positive stains due to contaminating antibodies to plasma proteins; and one (a monoclonal antibody) had many false negatives, probably due to its restricted antigenic specificity. Diagnosticians should be aware of the problems with false positive and false negative immunohistochemical stains. False positives in particular can be a significant problem, causing frequent misdiagnosis of hepatitis B.