We measured immunoreactive epidermal growth factor (EGF) by a homologous RIA in seminal plasma (SP) from 31 fertile and 52 infertile men to determine the relationship between SP EGF levels and total sperm count in the ejaculates. The mean SP EGF levels in fertile and infertile men were 41.7 +/- 21.5 (+/- SD) and 53.1 +/- 30.8 micrograms/L, respectively. Infertile men with sperm-associated immunoglobulin G (n = 9), immunoglobulin A (n = 6), or both (n = 8) had mean SP EGF levels of 48.9 +/- 26.1, 47.9 +/- 17.5, and 56.5 +/- 32.1 micrograms/L, respectively. Seven men with severe oligospermia had a mean SP EGF level of 58.5 +/- 35.9 micrograms/L. There was no correlation (r = 0.14; P greater than 0.05) between SP EGF levels and total sperm counts in these men. Fractionation of SP by high performance liquid chromatography on a size exclusion (TSK G2000 SW) column revealed a single immunoreactive peak with an approximate mol wt of 8000, slightly higher than the mol wt of circulating human EGF (6000). We conclude that SP EGF may be distinct from peripheral plasma EGF.