Immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum (CP), keyhole limpet hemocyanin (KLH) and an extract of Allium sativum (AS) was studied in a transitional cell carcinoma (MBT-2) in mice. Comparison was made between intraperitoneal (IP) versus intralesional (IL) administration of these agents. C3H/He mice were transplanted subcutaneously in the hind limb with 5 X 10(4) tumor cells. After transplantation, mice were randomized into groups to receive either IP or IL treatments with BCG (2 X 10(6) CFU), CP (250 micrograms.), KLH (50 micrograms.) or AS (25 mg.). At weekly intervals the tumor volume was determined. To assess the local cellular events following these treatments, histopathological studies were performed 10 days after tumor transplant with tissues removed from the injected sites. IL route was much more effective than IP route in inhibiting tumor growth. CP and AS exhibited more significant therapeutic effect than BCG or KLH. No tumor developed in mice which received five IL treatments of CP or AS. The data indicate that CP or AS may serve as effective biological response modifiers in controlling transitional cell carcinoma. The study further emphasizes that route and frequency of administration are crucial variables determining efficacy of immunotherapy.