Salivary glands of blood feeding insects such as the stable fly (Diptera: Muscidae) secrete a variety of proteins with antihemostatic activity. To understand the salivary gland transcriptome and proteome, 839 random clones from a stable fly salivary gland cDNA library were sequenced, and N-terminal sequences of the major proteins of salivary gland extracts were determined. The cDNA sequences were organized into 227 clusters of related sequences. The clusters were classified into three categories: unknown (57 clusters, 25% of the transcriptome), housekeeping (139 clusters, 61% of the transcriptome), and secretory (31 clusters, 14% of the transcriptome). Further analysis of putative secretory proteins revealed six serine proteases, three serine protease inhibitors, three antimicrobial peptides, an endonuclease, an immunoglubin-binding protein and thirteen clusters with no sequence similarity to any known proteins. Nine of these putative secretory proteins were confirmed by corresponding N-terminal sequences. To investigate the expression profiles of these secretory proteins, RT-PCR was conducted for nineteen mRNAs to test salivary gland specific expression, developmental regulation, and the impact of blood feeding. The most abundant protein in the salivary gland extracts, antigen 5, was found to bind nonspecifically to IgG, but not to F(ab^')₂ fragment of IgG. Antigen 5 may act to circumvent antibody-mediated damage from the complement system in host blood to stable fly tissue.