The immunobiology of heterotransplanted human tumors was investigated following transplantation into nude mice of human bronchogenic, colon, rectal, ovarian, gastric, endometrial, vaginal, bladder, renal, esophageal, embryonic cell, pancreatic, and breast carcinoma, as well as fibrosarcoma, rhabdomyosarcoma, malignant melanoma, astrocytoma, Wilms' tumor, endometrial hyperplasia, and hydatidiform mole. Several of these tumors were passaged up to 00 generations. During these passages no changes in latency period for tumor development or in histology were noted. There were significant differences between several tumors in the minimum number of cells required for successful transplantation; such differences were independent of the basic biologic aggressiveness of the individual tumors. Nude mice that received transplants of fibrosarcoma and endometrial carcinoma had increased serum IgM and numbers of spleen cells and complement receptor lymphocytes. No such changes were noted for mice that received transplants of malignant melanoma. In contrast, there were no apparent differences in the responses of nude mice, who were given transplants of human tumors, to the T-cell mitogens concanavalin A or phytohemagglutinin or in the number of theta-bearing spleen cells. The success rate for transplantation was significantly improved when explants, rather than single-cell suspensions, were performed. Tumors transplanted to nude mice derived from strictly homozygous matings behaved like tumors transplanted to mice born of heterozygous mothers. Finally, despite the dramatic size of subcutaneous tumor nodules, there were no examples of invasion or distant metastases.