The reported effectiveness of single tumor markers (TMs) associated with squamous cell cancer of the head and neck ranges from 15% to 71%, with most studies reporting sensitivity no higher than 50%. An increased incidence of the syndrome of inappropriate secretion of antidiuretic hormone or arginine vasopressin (SIADH) in patients with head and neck cancer has been reported. Serum arginine vasopressin (AVP) was studied as a possible TM in these patients. Sixty-three patients with squamous cell carcinoma of the head and neck determined as potentially curable were prospectively evaluated before treatment and compared to 17 patients with apparent cure of head and neck squamous cell cancer who served as controls. Serum AVP levels were obtained and determined by radioimmunoassay in the preoperative period and 1 week postoperatively in 15 patients. Thirty-four patients were staged as T4, 26 as T3, and 3 as T2. Twenty-one (33%) of the 63 patients had no neck involvement. Twenty-four (38%) of 63 patients had elevated serum AVP levels corrected for serum osmolarity. Of the 15 patients evaluated before and after surgery, 8(53%) had elevated serum AVP levels preoperatively. Of these 8 patients, 3 had reduction in AVP levels and 5 had complete normalizationafter 1 week. The results obtained for serum AVP do not exceed results of other TMs reported. AVP may also not be as specific as other TMs for cancer of the head and neck. Our group with AVP sampled postoperatively is too small for us to draw conclusions, but reduction of its levels after treatment in all patients may be significant. These preliminary results indicate that further evaluation of AVP during the posttreatment course in a larger number of cases, and perhaps with other TMs as well, is warranted.