With prostate cancer patients diagnosed between 1982 and 2000 (i.e., before and after prostate-specific antigen [PSA] screening became widespread), we specifically tested the following hypotheses: (1) lower plasma levels of 25(OH)D, 1,25(OH)2D, or both metabolites are associated with increased risk of prostate cancer, and the association is more pronounced for aggressive disease and among older men; and (2) men who carry the functional FokI f allele (which is less responsive to vitamin D signaling) have higher risk, especially if they have low vitamin D status. This evidence concerns the gene KLK3 and prostate cancer.