BACKGROUND: Valuable correlations could be made between serum prostate specific antigen (PSA) and prostate histopathology by the use of autopsy sampling if post-mortem PSA data were informative. However, PSA forms and levels in autopsy sera have not been investigated. MATERIALS AND METHODS: Paired ante- and post-mortem sera were collected for a series of cases. Total and free PSA levels in each were determined and compared. These PSA data were correlated with corresponding changes in serum electrolyte levels. RESULTS: Total PSA levels were similar in ante- and post-mortem sera if autopsy blood was drawn by approximately 24 hours following the time of death. Free PSA levels, however, were increased approximately two-fold in most post-mortem sera analyzed. Increases in the serum electrolytes potassium, magnesium and phosphate correlated positively with increases in free PSA. CONCLUSION: Total PSA levels in ante- and post-mortem sera were comparable. Free PSA levels had approximately doubled by autopsy, but may be normalized in relation to increases in serum electrolyte levels. The use of autopsy prostates and PSA data would avoid diagnostic bias from use of clinical material and permit extensive analysis to be carried out, which is not normally feasible with live subjects.