Peritoneal fluid from 35 women with endometriosis and from 34 control women was aspirated at laparoscopy and analyzed. No differences in prostanoid levels were found. The peritoneal fluid volume, macrophage concentration, macrophage content, and content of activated macrophages as measured by acid phosphatase staining were all significantly elevated in the endometriosis patients. The macrophages were incubated and the medium was added to the zona-free hamster egg sperm penetration assay. This medium caused a significant decrease in the percentage of ova penetrated in this assay. It is postulated that one of the mechanisms of infertility in women with endometriosis may involve the increased number of activated macrophages and their ability to interfere with sperm-egg interaction.