When local treatments for prostate cancer have failed, and prostate-specific antigen (PSA) rises in the absence of symptoms, there is little consensus as to the best management strategy. Calcitriol has been shown to prolong the doubling time of PSA in this context, but near-toxic doses are required. We investigated the effect of the nutrient vitamin D (cholecalciferol), a biochemical precursor of calcitriol, on PSA levels and the rate of rise of PSA in these patients. Fifteen patients were given 2,000 IU (50 microg) of cholecalciferol daily and monitored prospectively every 2-3 mo. In 9 patients, PSA levels decreased or remained unchanged after the commencement of cholecalciferol. This was sustained for as long as 21 mo. Also, there was a statistically significant decrease in the rate of PSA rise after administration of cholecalciferol (P = 0.005) compared with that before cholecalciferol. The median PSA doubling time increased from 14.3 mo prior to commencing cholecalciferol to 25 mo after commencing cholecalciferol. Fourteen of 15 patients had a prolongation of PSA doubling time after commencing cholecalciferol. There were no side effects reported by any patient. Further study is needed to confirm this finding and to explore the potential therapeutic benefit of nutrient vitamin D in prostate cancer.