Soluble TNFRs (tumour necrosis factor receptors) inhibit in-vivo and in-vitro bioactivities of TNF, and thus the secretion of soluble TNFRs could be a physiological principle to attenuate the bioactivities of TNF. Two types of TNFR have been identified and both forms can be released from cells. In this study, soluble TNFRs in seminal plasma from three groups of men were analysed: from men with normal semen quality (n = 32), with reduced semen quality (n = 7) and vasectomized men (n = 3). Sensitive and specific enzyme-linked immunosorbent assays were utilized to detect soluble TNFRs in seminal plasma, based on capture antibodies directed against non-TNF-binding sites of the TNFRs and digoxigenin (DIG)-labelled TNF. The mean +/- standard deviation levels of p55 TNFR were 56.4 +/- 20, 64.4 +/- 17 and 45.4 +/- 5 ng/ml in the three groups, respectively. The concentration of p75 TNFR was < 1 ng/ml in all groups. The results suggest an exclusive existence of high amounts of the soluble p55 TNFR in seminal plasma. Seminal plasma from vasectomized men contained p55 TNFR at approximately the same levels as the specimen from the two other groups, indicating that the source of p55 TNFR is not the testis but rather some tissue more distal in the male genital tract, such as the prostate or the seminal vesicles. The soluble p55 TNFR was purified from human seminal plasma, using affinity and gel filtration chromatography. Further characterization of the purified p55 revealed a protein with a molecular weight of approximately 22 kDa, both under reducing and non-reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)