Hemolymph of invertebrate animals contains many molecules involved in unique and effective innate defense systems against invading microbes. Their defense systems are activated by the recognition of common epitopes on pathogens, such as bacterial lipopolysaccharide (LPS), peptidoglycan, and fungal β-(1,3)-glucans. In the horseshoe crab (also called limulus), an arthropod, the hemocytes are extremely sensitive to LPS on the outer membrane of Gram-negative bacteria (1,2). In the presence of minute amounts of LPS, the hemocytes release coagulation factors, antimicrobial substances, and lectins by rapid exocytosis (3–6). The coagulation factors constitute two types of the coagulation cascade, each of which is sensitive to LPS or β-(1,3)-glucans (6–8). Thus, after the exocytosis induced by LPS, the coagulation factors are activated on the surface of the pathogens and the pathogens are immobilized in an insoluble hemolymph clot. The pathogens are then effectively agglutinated by various types of lectin/agglutinins and finally killed by antimicrobial substances (6,9,10).