The development of polycythemia after renal transplantation is a well known phenomenon and its etiology remains controversial. In particular, it is unknown whether inappropriate erythropoietin (EPO) production could be a reason. Utilizing a sensitive radioimmunoassay for EPO we have measured EPO concentrations in venous blood from native and grafted kidneys in three normocythemic and seven polycythemic patients. We found that (1) in our posttransplantation polycythemic patients there are inappropriately high systemic EPO levels, hence that posttransplantation polycythemia is related to EPO overproduction. (2) This high EPO production comes from the native kidneys. (3) There is a correlation between EPO and renin levels in the peripheral as well as in native and transplanted kidneys' venous samples.