Several studies have compared prostate-specific antigen (PSA) kinetics in men with and without cancer, but there has been no adequate analysis of the longitudinal variation in PSA. The aim of this study was to assess the fluctuations in PSA in a cohort of elderly men in an attempt to define a physiological pattern of PSA kinetics. We searched a specific cohort of patients aged > 75 years and with PSA value < 2.0 ng mL(-1). A history of all PSA values over the past 10 years was compiled for each patient to create a database of patients fitting the following criteria: (1) minimum of five PSA measurements, (2) over at least 5 years. Exclusion criteria were: (1) PSA < 0.2 ng mL(-1) at each measurement and (2) having had more than one PSA test per year. In all, 1 327 patients (mean age: 78.52 years) fit the inclusion criteria. The mean variation from the first to the last PSA test was 0.05 +/- 0.43, with a mean follow-up of 6.79 +/- 1.71 years. Over the same period, the mean fluctuation from the lowest to the highest PSA value was 0.04 +/- 0.55 (P = 0.925). The mean annual PSA velocity (PSAV) was calculated by dividing the mean variation from the first to the last PSA test by the number of years of observation for each patient and was set at 0.0104 +/- 0.1050. Concluding, in a large-scale cohort of elderly individuals considered healthy and evaluated for a considerable follow-up, the average annual PSAV as well as the average fluctuation from the lowest to the highest PSA value are insignificant.