BACKGROUND: Serum prostate-specific antigen (PSA) concentrations after radical prostatectomy typically become undetectable with the use of current immunometric assay methods. Despite modern surgical techniques, 15%-30% of prostate cancer patients undergoing radical prostatectomy develop a biochemical recurrence during follow-up. Unfortunately, poor analytical sensitivity of standard PSA assays delays biochemical recurrence detection, and because of day-today assay imprecision ultrasensitive PSA assays cannot assess PSA kinetics. We developed an immuno-PCR assay for total PSA that has a limit of quantification Ͼ10 times lower than current ultrasensitive assays.