Serum prostate specific antigen (PSA) is widely used for screening of prostate cancer, but little is known about its kinetics during development of the disease.Twenty-five prostate cancers were detected among 5908 middle aged men participating in a primary prevention trial for coronary heart disease. Two age matched control groups were chosen: 50 subjects each with BPH and without urologic symptoms, resp. During 1980–1986 blood samples were drawn at 3 mo intervals and 1986–1990 at 6–12 mo intervals.Serum PSA was ≥4μg/1 in 54% of samples drawn ≥4–<5 years before prostate cancer diagnosis. In samples from the same period the proportion was 28% among BPH patients and 3% among healthy controls. The respective proportions were 60%, 22% and 5% ≥2–<3 years before the diagnosis. In cancer patients the pattern of PSA kinetics was highly variable.PSA is a valuable tool for prostate cancer screening, but overlapping with other clinical conditions is considerable. Prostate cancer is a heterogenous malignancy, and this is reflected on variable PSA kinetics.