Sixty adults were tested for humoral and cell-mediated immunity to varicella zoster virus (VZV), type 1 herpes simplex virus (HSV-1) and the human cytomegalovirus (CMV). Since herpesviruses share common antigens, we compared results in these individuals to assess whether our tests gave false positives due to cross-reactions. Of the 60, IgG antibody to VZV, HSV-1, CMV tested by ELISA was detected in 51 (85%), 34 (57%) and 20 (33%) respectively. All possible permutations of results were obtained and there was no evidence of cross-reactivity among the viruses. Lymphocyte transformation performed in 20 was found to be positive in 16 (80%), 13 (65%) and 8 (40%) for VZV, HSV-1 and CMV respectively. Similarly, all possible permutations of results were obtained. In addition, 8 subjects were found to have positive lymphocyte transformation responses for one or other of the viral antigens but no specific antibody was found in their sera. Thus, the antibody and lymphocyte transformation test were not influenced by possible cross-reacting antigens among the 3 herpesviruses we studied. Both tests are necessary to firmly establish whether a subject has had a prior infection.