In vitro reactivity of normal lymphocytes in various sera was determined by quantitation of phytohemagglutinin (PHA)-induced tritiated thymidine incorporation rate (counts per minute). Sera were obtained from normal subjects, fetal calf, and patients with bladder carcinoma. The rate of lymphocyte blastogenesis was expressed as a stimulation index (SI) that was calculated by dividing the number of counts per minute with PHA by that without PHA. The effect of sera on blastogenesis of normal lymphocytes was expressed as percent change (%SI) per SI with fetal calf serum. The SI of normal lymphocytes was similar in autologous serum (26.7 +/- 11.6), fetal calf serum (25.4 +/- 11.8), and heat-inactivated homologous normal AB serum (28.8 +/- 11.4). The SI of normal lymphocytes in sera from patients with bladder carcinoma was significantly lower than in the other two sera (14.0 +/- 7.9). The serum inhibitory effect was significantly associated with the stage and grade of tumor and was diminished after removal of the tumor. The SI of lymphocytes from patients with certain other malignant diseases was significantly lower in autologous serum than in fetal calf serum or homologous normal AB serum. The SI of the lymphocytes from patients with prostatic carcinoma and embryonal cell carcinoma was also low in sera from patients with bladder carcinoma as well as in autologous sera. It is likely that the depressive effect of sera from patients with bladder carcinoma was not specific to bladder carcinoma.