A clinical trial was conducted to evaluate protracted systemic thiotepa as an adjuvant to radical mastectomy for treatment of operable carcinoma of the breast. Patients were randomized to have the operation (controls) or the operation plus a year of adjuvant therapy beginning at the time of surgery. Seventy-five controls and 90 treated patients have been observed from one to ten years. It was not possible to establish from this trial that thiotepa used in this manner was of value as a surgical adjuvant. Local recurrence was reduced but recurrence overall was not altered, either in its frequency or time of appearance. A notable trend associated with treatment was improved disease-free survival among treated patients without axillary metastases, suggesting that the adjuvant may be most effective when residual cancer is minimal.