Curative surgery diminished natural killer (NK) cell activity in 17 patients with previously untreated squamous cell carcinoma of the head and neck (37% +/- 17%, preoperatively vs. 21% +/- 11%, postoperatively; p less than 0.001). This operatively induced suppression was dependent on the presence of a nylon wool adherent cell population. With the removal of this surgically generated suppressor population from the in vitro assay, postoperative suppression of natural killer activity was significantly diminished (21% +/- 13%, vs. 30% +/- 23%, p less than 0.01). The capability of fully restoring postoperatively suppressed NK cell activity was subsequently demonstrated by the synergistic effect of removing a nylon wool adherent suppressor population and stimulating NK cells with a naturally occurring immunopotentiator, tuftsin (from 21% +/- 13% to 41% +/- 23%; p less than 0.0001). In utilizing biological response modifiers in the perioperative period in the cancer patient, the interaction of these agents and the surgically generated suppressor cell population needs to be considered.