In tick salivary glands, genes induced during blood feeding result in the expression of new proteins secreted into tick saliva. These proteins are potentially involved in modulation of vertebrate host immune and hemostatic responses. In this study, subtractive and full-length cDNA libraries were constructed by use of mRNA extracted from salivary glands of unfed and 5-day engorged Ixodes ricinus. Sequences from these 2 libraries were compared with European Molecular Biology Laboratory (EMBL)/GenBank databases, which led to their classification into 2 major groups. The first group comprises cDNAs that failed to match or showed low homology to genes of known function. The second group includes sequences that showed high homology to genes of known function--for example, anticoagulants, inhibitors of platelet aggregation, and immunomodulatory proteins. Analyses of corresponding proteins suggest that they may be secreted by salivary gland cells. To study the properties of the recombinant proteins, selected cDNAs were expressed in mammalian or bacterial systems.