Effect of prior cancer chemotherapy on human tumor-specific cytotoxicity in vitro in response to immunopotentiating biologic response modifiers. Tumor-specific cytotoxicity was measured in fresh human biopsy specimens by a modification of the differential staining cytotoxicity assay. ImuVert, a cytokine inducer derived from Serratia marcescens, which produces broad-spectrum activation of both macrophages and lymphocytes, was dramatically more effective when it was tested in tumors obtained from patients with previously treated, chemotherapy-responsive adenocarcinomas (breast and ovary) than when it was tested in tumors obtained from either previously untreated patients or previously treated patients with chemotherapy-refractory adenocarcinomas (colon, lung, pancreas, stomach, kidney, gallbladder, uterus, and prostate). Similar findings, relating to prior chemotherapy treatment status, were obtained for tumor necrosis factor and interferon gamma, but not for interleukin-2 or interferon alpha. On the basis of these findings and on other evidence in the literature, we speculate that response to chemotherapy produces massive release and processing of tumor antigens. We further speculate that this response leads to a state in which the human immune system is primed (via in situ vaccination) to respond to exogenous macrophage-activation signals with potent, specific antitumor effects. 