Objectives. To characterize the role of demographic and clinical parameters in the measurements of prostate-specific antigen (PSA), free PSA (fPSA), and percent free PSA (%fPSA). Methods. This was a cohort study of volunteers to a randomized screening trial. A central laboratory determined PSA and fPSA for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A baseline evaluation of free and total PSA was done for 7183 white, black, Asian, Hispanic, and other male volunteers, aged 55 to 74 years. Comparisons were made across racial and ethnic groups and across a set of clinical parameters from a baseline questionnaire.Results. The median levels of serum PSA were less than 2.1 ng/mL in each age-race grouping of the study participants. The levels of free and total PSA were higher in black (n = 868, 12%) participants than in white (n = 4995, 70%) and Asian (n = 849, 11.8%) participants. Individuals who identified themselves as ethnically Hispanic (n = 339, 4.7%) had median PSA levels higher than whites who were not Hispanic. The free and total PSA levels increased with age, particularly among men 70 to 74 years old. However, the %fPSA levels showed less variation among the four racial groups or by age. The free and total PSA levels were higher among those who had a history of benign prostatic disease. Conclusions. Demographic (age and race/ethnicity) and clinical (history of benign prostatic disease) variables had a moderate effect on the measures of PSA and fPSA and very little effect on %fPSA.