The three dimensional structures of human prostate specific antigen (PSA) and glandular kallikrein (hGK) were modeled based on porcine pancreatic kallikrein A. High sequence similarity and conserved framework of serine proteases enabled accurate modeling. The catalytic site region consisting of catalytic triad, residues forming oxyanion hole and main-chain substrate binding residues were conserved. The substrate specificity pocket of PSA resembles that of chymotrypsin and hGK is most related with tonin. The models were used to predict interactions with substrate and inhibitor molecules. The models are valuable in interpreting mutant and epitope mapping data as well as when modifying properties of the proteases or when developing diagnostic detection methods for prostatic cancer.