The serum half-life of prostate-specific antigen (PSA) after radical prostatectomy is about 3 days; to the authors' knowledge, the PSA half-life during radiation therapy (RT) has not been investigated with weekly serial measurements. To determine the rate of decline and the half-life of PSA, serial measurements were obtained during 6-8 weeks of external-beam RT for localized prostate cancer. PSA values were determined immediately before and approximately 24 hours after the first dose of RT; thereafter, weekly measurements were made. There was a downward trend in PSA levels in 19 patients, with a median half-life of 58.5 days; the mean decline was 1.6% per day. However, in four patients, PSA levels either rose and fell to pre-RT values or increased steadily. The effect of digital rectal examination (DRE) on PSA levels was also analyzed. When the dates of DRE and subsequent PSA levels were inspected, no increase in PSA levels subsequent to DRE was found, although three of the four patients in whom PSA levels did not decrease underwent multiple DREs. The authors found a statistically significant (P = .023) transient elevation in the mean PSA values after the first fraction of RT (2 Gy) was administered; the mechanism and importance of which are not known.