A preliminary study of the response to various immunotherapy models in a spontaneous murine nal cell carcinoma model is reported. Tumor cells were implanted intrarenally and nephrectomy performed at a later time. Specific immunotherapy using irradiated whole tumor cells plus complete Freund's adjuvant and a crude membrane preparation plus the same adjuvant were compared to nonspecific immunotherapy with adjuvant alone. In the 1st of 2 response criteria examined, there was a statistically significant decrease in tumor growth following hind limb rechallenge in those animals immunized with the membrane preparation plus adjuvant (p less than 0.01). This form of therapy also produced a statistically significant (p = .024) increase in survival in a second experimental model in which locally recurrent tumor was induced. Whole irradiated cells plus adjuvant slightly enhanced tumor growth, while adjuvant alone had no effect. Treatment with adjuvant alone did, however, result in an increase in the incidence of pulmonary metastases in both groups of animals. The practical and theoretical applicability of a membrane preparation vaccine in human tumors is discussed.