Numerous growth factors have been identified for lung cancer including bombesin, neurotensin, insulin-like growth factor I, transforming growth factor a and vasoactive intestinal peptide. These growth factors are secreted from lung cancer cells into biological fluids. Here proteins in the 1,000-20,000 dalton range were characterized in frozen lung cancer biological specimens using surface enhanced laser desorption/ionization (SELDI) techniques. Lung cancer sections were microdissected using laser capture microdissection techniques. Proteins were extracted from 10,000 cells using 6 N guanidine.HCl. The extracts were absorbed onto an H4 chip and fractionated by SELDI analysis. In tumor specimens, numerous proteins were identified with mass/charge ratios of 3,195-3,772 daltons. One of the proteins had a molecular weight of 3372. This protein was purified using high pressure liquid chromatography techniques and identified as defensin, human neutophil protein 2. In adjacent normal specimens, these proteins were present with 5-fold lower densities, however, the normal specimens had a higher density of proteins in the 5,500-15,842 dalton range. It remains to be determined if defensins will serve as biomarkers for lung carcinogenesis.