The occurrence of multiple primary malignant neoplasms in single individuals is well documented. Although many hypotheses have been advanced to explain this occurrence, there has been no study to determine if a presumed "increased susceptibility to cancer" has an immunogenetic basis. We evaluated the cellular immunity and histocompatibility antigens of 42 patients who had had from two to four multiple primary malignant neoplasms. We failed to demonstrate a preexisting impairment of immunocompetence or abnormal HL-A antigen frequencies in these patients. The occurrence of multiple primary malignant neoplasms in related tissues, eg, lung/larynx/oral cavity, and the occurrence of successive primary malignant neoplasms at a time interval consistent with the patient's being cured of preceding malignant neoplasms suggest that multiple primary malignant neoplasms result from repetitive induction by the same or similar etiologic factors in patients who are cured after treatment of the first malignant neoplasm.