The Madison 109 lung carcinoma (M109) was evaluated as a model for the screening of antitumor agents. Thirty-five drugs with established antitumor activity were assayed in mice implanted ip or sc with M109. Depending on the mode of tumor implantation, drugs representing those affecting nucleic acids (through binding, interacalating, or inducing single-strand breaks), various alkylating agents, mitotic inhibitors, antimetabolites, and immunomodulators were able either to inhibit the growth of sc M109 or to extend the lifespan of mice given M109 ip. The ip implanted tumor was, for example, markedly affected (median survival time of treated/control mice, x 100: greater than or equal to 200% with occasional cures) by doxorubicin, mitomycin C, 10-hydroxy camptothecin, and dihydroxyanthraquinone. The sc implanted tumor, however, was markedly affected (treated - control of greater than or equal to 12 days with regard to median time to grow 1-g tumors) by bleomycin and an analog, talisomycin, and by 6-thioguanine. The M109 was responsive to many different classes of clinically active agents and can serve as a useful tool in the screening of drugs with such potential. It may be particularly useful in screening analogs of camptothecins, nitrosoureas, bleomycins, and mitomycins as well as for evaluating anthraquinones, anthracyclines, mitotic inhibitors, antimetabolites, and immunomodulators.