The ubiquitin-proteasome is an ubiquitous system mainly devoted to protein degradation. The presence of ubiquitinated proteins in male gametes suggests a role for this system also in reproduction. Available evidence indicate that ubiquitin in spermatozoa may have a role in semen quality control, as ubiquitinated defective spermatozoa in the epididymis are subsequently phagocytosed by epididymal epithelial cells. Moreover, a role both in the regulation of mitochondrial inheritance in mammals (paternal mitochondria are eliminated and their ubiquitination appears to be important for this process) and in sperm-oocyte interaction at fertilization (which is inhibited by an inhibitor of proteasome) have been also suggested. We found that both morphologically normal and abnormal human spermatozoa in semen may be ubiquitinated and that the percentage of ubiquitinated sperm in the ejaculate positively correlates with normal morphology and motility, suggesting that sperm ubiquitination may have a positive role in sperm functions. It remains to be defined if and which patterns of ubiquitination of spermatozoa may distinguish between the different biological functions of this system. In an attempt to answer this question, we set up a method to detect simultaneously ubiquitination and DNA fragmentation by FACScan since the latter parameter is related to a poor quality of semen; in particular, abnormal morphology. We found that DNA fragmented human spermatozoa are also ubiquitinated. Studies are in progress to determine the correlation between the fraction of ubiquitinated-non DNA fragmented spermatozoa and parameters of semen analysis.