We report here the isolation from plasma of two penaeid shrimp species of novel peptides/polypeptides with exclusive antifungal activities. A set of three molecules was purified with molecular masses at 2.7 kDa (Penaeus vannamei), 7.9 kDa, and 8.3 kDa (Penaeus stylirostris). Primary structure determination was performed by a combination of Edman degradation and mass spectrometry. The peptides display 95-100% sequence identity with a C-terminal sequence of hemocyanin, indicating that they are cleaved fragments of the shrimp respiratory protein. Specific immunodetection of the hemocyanin-derived (poly)peptides revealed that experimental microbial infections increase their relative concentration in plasma as compared with nonstimulated animals. Thus, the production of antifungal (poly)peptides by limited proteolysis of hemocyanin could be relevant to a shrimp immune reaction that would confer a new function to the multifunctional respiratory pigment of crustaceans.