One hundred four consecutive men who underwent a semen analysis as part of their infertility evaluation were assayed for sperm-associated immunoglobulin (Ig) and the third component of complement (C3). Sixteen (15%) of the 104 men had increased IgG, and 10 (12%) of 86 men tested had increased IgA on their sperm; however, only 4 (5%) of the 87 men tested were positive for plasma IgG antisperm antibody. Only 2 (13%) of the 16 men with increased sperm-associated IgG had detectable IgG antisperm antibodies in their seminal plasma. Five (10%) of 50 men tested had increased sperm-associated C3; none had seminal plasma that deposited C3 on sperm. These data suggest that of the three compartments that can be tested--circulating plasma, seminal plasma, and the sperm surface--the direct measurement of sperm surface Ig may be most important in the evaluation of infertile men. The presence of sperm-associated IgG or IgA was not associated with semen abnormality. In contrast, the presence of sperm-associated IgG was associated with decreased mucus penetration at the time of postcoital testing despite normal-appearing mucus.