The saliva of patients with oral squamous cell carcinoma was subjected to reversed-phase HPLC, and a peak (P 14) was eluted with a linear gradient of acetonitrile. The molecular weight of P14 was 3,442 daltons by mass spectrometry. The results of amino acid sequencing by Edman degradation and homology studies indicated that P14 was consistent with a peptide, human alpha-defensin 1 (HNP-1) which belongs to the defensin family. The concentration of HNP-1 in the saliva of 6 squamous cell carcinoma patients before surgery and 11 after surgery was 12.3 +/- 8.6 and 6.5 +/- 5.9 micrograms/ml (mean +/- S.D.), respectively. In contrast, minimal amounts of HNP-1 were found in the saliva of adenocarcinoma patients and healthy volunteers. The concentration of salivary HNP-1 correlated positively with serum squamous cell carcinoma related antigen (SCC-Ag)level (r = 0.879, p < 0.01).