Circulating prostaglandins, including thromboxane A2 and prostacyclin, have been implicated as possible facilitative agents in the growth and dissemination of squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the relationship of plasma concentrations of these compounds to tumor stage and the effect of surgical resection on plasma prostaglandin levels. Blood samples were obtained from 40 patients with head and neck cancer. Ten treated patients were clinically disease-free (NED), and 30 patients with active disease were previously untreated at the time of this study. Plasma concentrations of thromboxane A2 and prostacyclin were measured by radioimmunoassay of their stable metabolites thromboxane B2 (TxB) and prostaglandin 6-keto-Fl (PGI). Platelet aggregation was performed with normal donor platelets (PRP) and normal control or patient plasma (PPP). TxB and TxB/PGI ratios were increased in TlNOMO patients, compared with NED and with T4NOMO primary lesions versus all other groups. With lymphatic and hematogenous metastases, TxB and TxB/PGI ratios fell to NED levels. ADP-induced platelet aggregation was significantly increased in head and neck cancer patients, compared with normal controls, and with T4NOMO lesions, compared with NED. There were no significant differences in PGI levels. TxB, PGI, TxB/PGI, and platelet aggregometry did not change significantly with curative surgery. TxB and TxB/PGI interactions are involved in head and neck cancer. Changes in TxB and TxBlPGI may be related to increased platelet aggregation. KEY WORDS: thromboxane Az, prostacyclin, head and neck cancer, prostaglandins, cancer, tumor growth Recent studies have suggested more specifically the