Despite vast efforts and expenditures in the past few decades, malaria continues 
to kill millions of persons every year, and new approaches for disease control 
are urgently needed. To complete its life cycle in the mosquito, Plasmodium, the 
causative agent of malaria, has to traverse the epithelia of the midgut and 
salivary glands. Although strong circumstantial evidence indicates that parasite 
interactions with the two organs are specific, hardly any information is 
available about the interacting molecules. By use of a phage display library, we 
identified a 12-aa peptide--salivary gland and midgut peptide 1 (SM1)--that 
binds to the distal lobes of the salivary gland and to the luminal side of the 
midgut epithelium, but not to the midgut surface facing the hemolymph or to 
ovaries. The coincidence of the tissues with which parasites and the SM1 peptide 
interact suggested that the parasite and peptide recognize the same surface 
ligand. In support of this hypothesis, the SM1 peptide strongly inhibited 
Plasmodium invasion of salivary gland and midgut epithelia. These experiments 
suggest a new strategy for the genetic manipulation of mosquito vectorial 
capacity.