Protein concentrations of seminal plasma and spermatozoa were estimated in human normospermic, oligospermic and azoospermic semens. The protein content of seminal plasma ranged from 20 to 60 mg per ml semen and was found to be unrelated to sperm counts. Suspended sediments of azoospermic specimens were found to contain on the average 570+/-86 microng protein per ml semen. This value is about four times higher than in severe oligospermic specimens (0.2 X 10(6) -6.5 X 10(6) cells per ml semen). It is suggested that in azoospermic disorders seminiferous tubules secrete abnormally high amounts of proteinacous material which cannot be eliminated by washings. In addition, destruction of immature cells may contribute to increased protein conten in these specimens. Protein determinations in washed spermatozoa showed a negative relationship between the amount of protein calculated per 10(6) cells and original sperm counts. This trend demonstrates an altered protein metabolism in the spermatozoa of oligospermic specimens which might be responsible for fertility incompetence.