Objective: To determine whether anionic ligands for the macrophage scavenger receptor inhibit the fertilization of mouse oocytes by mouse spermatozoa. Design: In vitro study of sperm binding and two-cell embryo formation in the presence of scavenger receptor ligands. Sperm-oocyte interaction may be mediated by sulfated sugars. In this study, we tested other nonsulfated anionic ligands for the scavenger receptor for their ability to affect fertilization. The only common feature of these ligands is their anionic nature. Setting: Oocytes and sperm from mice were used. Main Outcome Measure(s): Binding of sperm to oocytes and subsequent formation of two-cell embryos were determined. Result(s): Fucoidin, polyinosinic acid, oxidized low-density lipoprotein, acetyl low-density lipoprotein, and malondialdehyde-modified LDL inhibited the binding and fertilization of mouse sperm to mouse oocytes. Addition of fresh sperm to oocytes previously treated with sperm in the presence of these agents restored the binding and fertilization. Conclusion(s): These results show that charge-based interactions analogous to the interactions of the scavenger receptor with its ligands may play an important role in mammalian fertilization.