To date, little attention has been paid to the possible role of alpha-defensins (human neutrophil peptides 1-3), HNP-1, HNP-2 and HNP-3 in innate host defence against tumour invasion. In the current study, using a single-dimensional high pressure liquid chromatography (HPLC) method for peptide separation, followed by mass spectrometry and amino acid sequencing for identification and quantitation, we report the overexpression of HNP-1, HNP-2 and HNP-3 in squamous cell carcinomas of the human tongue compared with autogenous non-tumour tissue. Using a specific antibody we show that the defensins are abundant in neutrophils infiltrating human oral squamous cell carcinoma tissue. In the context of their previously reported oncolytic activity, our results may imply a role for alpha-defensins in host defence against oral squamous cell carcinoma.