The serum level of tumor-antigen 4 (TA-4) was measured in 401 patients with squamous cell carcinoma (SCC) of various organs (76 lung, 82 esophagus, and 234 head and neck). The mean serum level of TA-4 in patients with lung SCC was 3.6 times higher than that in healthy controls and even higher in the advanced stages of disease (III, IV). In patients with benign diseases or other types of lung cancer, however, the TA-4 serum level was not different from the controls regardless of the clinical stage. During radiation therapy, the TA-4 levels in patients with lung SCC decreased with reduction in tumor size. It increased again markedly during recurrence. Similarly, patients with SCC of the esophagus and head and neck also showed elevated TA-4 levels but only at advanced stages and in recurrence. It was concluded that TA-4 is highly related to SCC not only of the uterine cervix but also of other organs and that serum level determinations are useful for monitoring therapeutic effects and recurrence of these diseases, despite some limitations.