Antimicrobial lipids are found in mucosal secretions and are one of a number of nonimmunologic and nonspecific protective factors found at mucosal surfaces. Lipids can inactivate enveloped viruses, bacteria, fungi, and protozoa. Lipid-dependent antimicrobial activity at mucosal surfaces is due to certain monoglycerides and fatty acids that are released from triglycerides by lipolytic activity. Medium chain length antiviral lipids can be added to human blood products that contain HIV-1 and HIV-2 and reduce the cell-free virus concentration by as much as 11 log10 TCID50/ml. The presence of lipids does not interfere with most clinical assays performed on human blood samples. Antimicrobial lipids can disrupt cell membranes and therefore lyse leukocytes which potentially carry virus. Genital mucosal epithelial cells should be protected from damage by the mucous layer. Preliminary studies indicate that lipids decrease sperm motility and viability suggesting that lipids may potentially be used as combination spermicidal and virucidal agents.