Cytokines play an important role in intercellular communications. Human sperm contains a wide spectrum of cytokines, such as interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). Their effects on semen quality are subject to debate. The aim of this study was to determine concentrations of IL-1beta and TNF-alpha in normal fertile men and in different groups of male infertility in an attempt to clarify the physiology and suggest possible clinical uses. Sixty-six subfertile male patients with varicocele (n = 22), infection of accessory genital glands (n = 14), varicocele plus infection (it = 4), chronic epididymitis (n = 8), post-renal transplantation status (n = 5), idiopathic oligoasthenoteratospermia (n = 9), cryptorchidism (n = 1), and homozygous beta-thalassemia (it = 3) as well as 5 male controls were studied through history, physical examination, spermiograms, plasma basal hormonal levels, and IL-1beta and TNF-alpha levels in seminal fluid. There was no significant statistical difference regarding IL-1beta and TNF-alpha among fertile men and subfertile patients of any cause, lL-1beta and TNF-alpha were in tight positive correlation (P<.001). Determination of IL-1beta and TNF-alpha does not provide useful information in male routine infertility workup, Nevertheless, a better understanding of these mediators in semen of normal men and infertile patients may contribute to a new approach to the management of male infertility.