The human kallikrein (hk) family, located on chromosome 19, encodes prostate-specific antigen (PSA [or hK3]), hK2, hK4, and hK15 (prostin), as well as other serine proteases. Although PSA has been used in the detection of prostate cancer for several years, much remains unknown about its function and forms. The regulatory mechanisms of PSA are vital to its understanding. A particular mechanism by which PSA forms complexes with either alpha1-antichymotrypsin or alpha2-macroglobulin may provide important information for disease detection and progression. Data are emerging that show that active hK2, hK4, and hK15 may be important to convert pro-PSA to the active PSA enzyme. This information, along with insights into the precise mechanisms of PSA expression, may be used to suggest that PSA and, perhaps, other members of the hK family contribute critical control mechanisms to tumor invasion or progression. Although much remains to be revealed on the role of these gene products in the detection and progression of prostate cancer, findings from studies that show sensitive signaling of the disease > or =20 years before the diagnosis of clinically significant prostate cancer may alter screening procedures and improve treatment options.