In vivo and in vitro observations of cellular immune response in 70 patients with squamous cell cancer of the oral cavity and in 40 age-matched normal controls, were made using delayed hypersensitivity responses to DNCB, PPD, and Candida albicans extract (Dermatophytin 'O'), absolute lymphocyte counts, absolute T-cell numbers, and PHA-induced lymphocyte blastogenesis reactions as parameters. The results were correlated with clinical stage, tumor size, lymph node involvement, tumor differentiation, lymphoreticular responses, and outcome during a one-year follow-up period. A significant degree of impairment of both in vivo and in vitro parameters was found in oral cancer patients compared to normal control. The impairment was more prominent in advanced stages. Lymph node involvement was associated with impaired dermal hypersensitivity to recall antigens as well as a reduced T-cell population and blastogenic response. Only delayed hypersensitivity response to DNCB, PPD, and Candida showed a correlation with histologic features such as tumor differentiation and lymphoreticular response. Although absolute lymphocyte counts and T-cell population were reduced in the primary stage of the disease, the functional capacity of isolated lymphocytes to undergo blast formation was retained. PHA-induced lymphocyte blastogenesis showed a significant impairment only when the tumor was well established and disseminated beyond its local confines. Delayed hypersensitivity responses to DNCB, higher T-cell counts, and blastogenic indices were associated with recurrence-free survival. Immunologic parameters provide prognostic information beyond the clinical stage of the disease. Therefore, it seems that a multiparametric in vivo and in vitro observation of cellular immune response may be useful as an indicator of clinical course and prognosis of patients with squamous cell cancer of the oral cavity.