Peptidoglycans from bacterial cell walls trigger immune responses in insects and mammals. A peptidoglycan recognition protein, PGRP, has been cloned from moths as well as vertebrates and has been shown to participate in peptidoglycan-mediated activation of prophenoloxidase in the silk moth. Here we report thatDrosophilaexpresses 12PGRPgenes, distributed in 8 chromosomal loci on the 3 major chromosomes. By analyzing cDNA clones and genomic databases, we grouped them into two classes:PGRP-SA, SB1, SB2, SC1A, SC1B, SC2,andSD, with short transcripts and short 5′-untranslated regions; andPGRP-LA, LB, LC, LD,andLE, with long transcripts and long 5′-untranslated regions. The predicted structures indicate that the first group encodes extracellular proteins and the second group, intracellular and membrane-spanning proteins. MostPGRPgenes are expressed in all postembryonic stages. Peptidoglycan injections strongly induce five of the genes. Transcripts from the differentPGRPgenes were found in immune competent organs such as fat body, gut, and hemocytes. We demonstrate that at leastPGRP-SAandSC1Bcan bind peptidoglycan, and a function in immunity is likely for this family.