Placental protein 5 (PP5)-like immunoreactive material was detected in human seminal plasma at high concentrations (32-1000 ng/ml). This was not due to interference with proteases or binding to seminal plasma proteins, since immunoreactivity was not affected by treatment with protease inhibitors, and incubation with seminal plasma of [125I]PP5 did not bring about any significant change in the elution pattern in gel filtration. Part of the PP5 immunoreactivity in seminal plasma had a molecular weight of 36,000-42,500 which is the molecular weight of purified PP5 from the human placenta. In RIa, serial dilutions of the 36,000-42,500 molecular weight material gave an inhibition curve parallel to that of the PP5 standard. The source of seminal plasma PP5-like material is not from the testes, as the levels in vasectomized men were similar to those in nonvasectomized men.