The mechanisms of action of the specific active immunotherapy of solid tumors have not been defined. In an attempt to characterize some of these mechanisms, we report controlled studies of humoral immune responses and cell-mediated immune (CMI) responses in lung cancer patients with Stage I and Stage II adenocarcinoma and squamous cell cancer receiving pure tumor-associated antigen (TAA) specific active immunotherapy or combination immunochemotherapy. At 5 to 6 months postimmunotherapy, the humoral immune response measurements are predictive of response to therapy/survival in early lung cancer patients, permitting decisions as to whether to continue therapy. Patients with adenocarcinoma respond to combination chemoimmunotherapy by showing stronger or earlier responses to tests of immunity. Cell-mediated immunity to TAA at 17 to 24 months was far greater in patients receiving immunotherapy or immunochemotherapy compared with control patients, and also correlated with early humoral immune response and with 5-year survival. Here we report a further subset analysis of Stage I and Stage II lung cancer patients in a successful Phase III US specific active immunotherapy trial as substantiating the experience with Stage I patients in a successful Phase II Canadian trial. We analyze failures and suggest additional therapies, especially a chemoimmunotherapy trial indicated by our analyses of humorocellular immune variables reported here.