Human seminal plasma (SP) contains potent complement inhibitors. This study examined the complement-inhibiting activity of individual SP samples from 118 patients with infertility and analyzed them in relation to various semen parameters. When 25% complement-inhibiting activity was considered the cut off value, less than 1 SD unit from the mean percentage of inhibition of SP samples with normal semen quality, 32 samples (27%) showed low inhibiting activity. Among the lower group, incidences of patients with asthenozoospermia (66%) and oligozoospermia (31%) were significantly (p < .01) higher than those (36 and 10%) in the group whose SP showed significant inhibiting activity. Partial characterization revealed that the component responsible for complement inhibition was heat labile, trypsin resistant, high molecular weight (>10 kD) glycoprotein that can inhibit alternative as well as classical complement pathways. Furthermore, since in the majority of SP samples the anticomplementary activity was blocked by monoclonal antibody against membrane cofactor protein (MCP) or decay accelerating factor (DAF), the complement-inhibiting factors that were identified are likely to be MCP and/or DAF, which are known to be present in human SP. These results suggest that complement-regulatory proteins in SP such as MCP and DAF may protect sperm cells against complement attack in the male reproductive tract.