The effects of human recombinant epidermal growth factor (EGF) on the fertilizing capacity of human sperm were investigated. At lower concentrations (0.1-10 nM) EGF did not significantly (P > 0.05) affect human sperm penetration of zona-free hamster oocytes (SPA). At higher concentrations (25-100 nM), EGF significantly (P = 0.01 to < 0.001) decreased the human sperm penetration rates in SPA. At higher concentrations (> or = 25 nM), EGF also significantly inhibited the spontaneous as well as calcium ionophore-induced acrosome reaction and release of acrosin from human sperm. There was no effect of EGF on percent sperm motility, but at higher concentrations (> or = 25 nM) it significantly affected various sperm motility characteristics especially velocity and amplitude of lateral head displacement. EGF was detected by radioimmunoassay as well as radioreceptor assay in seminal plasma of fertile men. However, there were no statistical differences between the levels of EGF or EGF/transforming growth factor (TGF-alpha) in seminal plasma of fertile, infertile, and immunoinfertile men. Also, there was no significant correlation of the EGF or EGF/TGF-alpha levels with total sperm number, sperm motility characteristics, and penetration rates in SPA in these patients. These results indicate that EGF has either no effect or an inhibitory/negative effect on the human sperm cell capacitation and/or acrosome reaction, especially at higher concentrations (> 25 nM).