The cytotoxicity in vitro of peripheral blood lymphocytes from 54 patients with transitional cell carcinoma of the urinary bladder (TCC-bladder) against a small panel of allogeneic target cells was studied by the "'Cr-release assay. Lymphocytes f r o m 20 patients with other neoplastic diseases, mainly urogenital cancers, were used as controls. Also included were lymphocytes from 24 healthy donors. Lymphocytes f r o m individual donors of all three groups were frequently cytotoxic t o any one of the target cell types on the panel and occasionally this cytotoxicity was high. However, lymphocytes f r o m TCC-bladder patients who were untreated for their disease had an elevated mean cytotoxicity against cells from t w o different cell lines of TCC-bladder origin as compared with that against other target cells, derived either from normal bladder epithelium, from colon qarcinoma o r from malignant melanoma. The cytotoxicity against TCC-bladder targets of lymphocytes from the clinical controls (who were untreated for their cancer) was not significantly elevated over that against the other targets. The same was true for the healthy donors. Lymphocytes f r o m TCC-bladder patients treated with radiotherapy f r o m 1-12 years before testing also had an elevated mean cytotoxicity against TCCbladder targets. This group (31 patients) was heterogeneous, comprising patients with a generally reduced cytotoxicity and others whose lymphocytes were strongly cytotoxic t o TCC-targets. However, while no correlations between cytotoxlcity t o TCCbladder targets and targets of other origin were seen for the untreated patients, the treated TCC-bladder patients showed a positive correlation between cytotoxicity t o TCC-bladder targets and normal " bladder targets. Taken together, the results indicate that lymphocytes of most (but not all) donors was selective, i.e. individual donors' lymphocytes were cytotoxic for some target cell types but not for others. Inspection of cytotoxicity profiles suggests that these selective reactions reflect multifactorial immune responses against a variety of antigens. In addition, in TCC-bladder patients there exists a superimposed cytotoxicity, probably reflecting reactions against one o r several tumor-associated antigens. In treated patients this may be masked by a higher incidence o f cross-reactions, o r by a generally suppressed reactivity. Finally, the results also emphasize the importance of using age-and sexmatched controls for assessing the relative cytotoxicity of different groups of lymphocyte donors.