A new method of baccile Calmette Guérin (BCG) immunotherapy has been evaluated in 25 patients with lung cancer. This technique involves the direct intratumor injection of BCG in patients with pulmonary tumors. Four patients underwent transbronchoscopic injections of tumor, with significant resolution of tumor in three. Twenty-one patients underwent percutaneous injection with the aid of fluoroscopic imaging. Twenty of these 21 underwent pulmonary resection. Toxicity was limited to fever and malaise. The severity of this toxicity was closely related to the magnitude of reactivity to PPD. There were no intraoperative or postoperative complications occasioned by BCG injection. The histologic features were characterized by granulomatous inflammatory reactions in the tumors and the regional lymph nodes. These histologic findings are identical to those seen in animal tumor models in which potent systemic antitumor immunity is induced. BCG intratumor injection is technically feasible and safe, and it is appropriate to begin phase 2 and phase 3 clinical trials.