A series of 6 controlled experiments in C3H/He mice were performed to evaluate nonspecific immunotherapeutic regimens with a transplantable murine bladder tumor (MBT2). Immunotherapeutic agents studied included live Bacillus Calmette-Guerin (BCG) preparations in varying doses and strains (Tice, Pasteur, and Glaxo), Re mutant glycolipid (ReG) from Salmonella typhimurium, BCG cell wall skeletons (CWS), CWS plus B4 glycolipid fraction of ReG, and Keyhole-Limpet Hemocyanin (KLH). Animals received an intradermal MBT2 inoculation and were then randomized to treatment and control (saline treated) groups. Immunotherapy was administered intralesionally 1 day after tumor transplantation. Tumors were excised by amputation at a volume of 400 mm. and animals were later rechallenged with tumor inocula, again treated, and followed for tumor incidence growth rate and survival. No antitumor affect was observed with ReG, CWS or CWS plus B4. KLH immunotherapy did result in measurable antitumor effect. Consistent and statistically significant (p less than 0.01) antitumor responses as measured by prolonged survival and decreased growth rate were observed with Tice and Pasteur strains of BCG in doses ranging from 5 X 10(5) to 1 X 10(7) colony forming units per animal. Doses in excess of 10(7) units were found to decrease antitumor response. Glaxo strain BCG had no beneficial effect when used in the maximal dose (10(6) colony forming units) that could be administered. In animals immunized with intermediate doses of live Tice or Pasteur strain BCG in the study, effective long term immunity to transitional cell carcinoma was observed. Although many new immunotherapeutic agents have been advocated in other tumor models, to date we have found Tice and Pasteur strains of live BCG to be the most effective agents in the treatment of transitional cell carcinoma.