The results of the present studies demonstrate that intramuscular injections of polyestradiol phosphate (PEP) produce not only considerably increased estrogen concentration in plasma but also maintain the same estrone/estradiol ratio as in normal men. Monthly injections of PEP produce persistent elevation of the plasma estradiol levels throughout the dose interval, and rising PEP doses produce proportionately increasing steady-state plasma concentrations of estradiol. The steady-state plasma concentrations of testosterone are reduced to 45, 25, and 15% of the pretreatment concentrations after treatment every fourth week with 80, 160, and 240 mg PEP, respectively.