We studied the relationship of natural killer activity from peripheral blood mononuclear cells with clinical stage of disease and the different modalities of treatment in 67 untreated patients with transitional cell carcinoma of the bladder and 29 normal controls. Peripheral blood mononuclear cells from 39 patients with superficial bladder tumor (stages Ta and T1) showed a natural killer cell activity similar to that of controls (p greater than 0.05), while in 28 patients with infiltrating tumors (stages T2, T3 and T4) this activity was significantly depressed (p less than 0.01). This functional phenomenon cannot be ascribed to a deficient number of natural killer cells in patients with infiltrating tumors, since the amounts of HNK-1+ (Leu 7), CD16+ (Leu 11) and CD11b+ (OKM1) cells in peripheral blood mononuclear cells were similar in the 3 groups of subjects (p greater than 0.05). Furthermore, the natural killer activity of peripheral blood mononuclear cells was normal (p greater than 0.05) in patients who underwent transurethral resection of the tumors and intracavitary cytostatic therapy with doxorubicin who remained free of disease at least 6 months after treatment. However, in patients with superficial recurrent tumor a significant decrease in the natural killer activity of peripheral blood mononuclear cells was observed (p less than 0.05), which was more pronounced in those with infiltrating recurrence. Also, in the latter patients total cystoprostatectomy was associated with a relevant increase in the spontaneous level of peripheral blood mononuclear cells. We conclude that in patients with transitional cell carcinoma of the bladder there is a correlation of the levels of natural killer activity in peripheral blood mononuclear cells with clinical evolution and pathological stage of disease. The determination of this activity is useful to monitor patients with transitional cell carcinoma of the bladder.