An evaluation of natural killer cell activity was performed in 42 patients with pharyngeal carcinoma. Compared with age- and sex-matched control subjects, the cancer patients expressed significantly lower cytotoxicity against K562 target cells (68 +/- 8 lytic units versus 99 +/- 8 lytic units, p less than 0.01), with 52 percent of the patients expressing deficient activity (below 1 standard deviation of the mean activity of the control population). The probability of deficient activity was greater in these patients than observed in patients with cancer of other head and neck sites. Although natural killer cell activity was lower in patients who drank alcohol or had nodal metastases, no single clinical factor was predictive of deficient cytotoxic response. Prospective longitudinal evaluation (mean = 12 months) of these pharyngeal cancer patients demonstrated that deficient natural killer cell activity measured before treatment identified a population with a significantly increased risk for the development of distant metastases. Distant metastases developed in 7 of 18 patients (39 percent) with deficient natural killer cell activity. In contrast, none of the 16 patients with normal natural killer cell function had evidence of distant disease at last follow-up (p less than 0.01). Deficient natural killer cell activity exists in patients with pharyngeal cancer and is an independent marker for the subsequent development of distant metastases.