Cell-mediated immunity to herpes simplex virus and cytomegalovirus, using the lymphocyte transformation test and interferon induction in lymphocytes, was studied in 59 patients from 1 day to 7 years after allotransplantation and compared with the results in normal subjects. Both parameters were permanently depressed with regard to cytomegalovirus. With herpes simplex virus, interferon production was also permanently depressed, whereas the transformation reaction was normal during the first year after transplantation and only slightly depressed in patients more than 1 year after transplantation. In 6 patients the above-mentioned assays and the complement fixation reaction were performed serially and related to the clinical signs of herpes simplex virus and cytomegalovirus infection. The relationship between depression of the transformation reaction and interferon production in lymphocytes and the occurrence of clinically evident herpes simplex virus and cytomegalovirus infections was, however, equivocal. The humoral immune response to herpes simplex virus was measured by the complement fixation test and the more sensitive antibody-dependent, cell-mediated cytotoxicity reaction, and a good correlation was found between these two tests, although only a few persons were found to be negative in the antibody-dependent, cell-mediated cytotoxicity reaction. The suggestion is made that only a few adults are "true" herpes simplex virus seronegative.