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This project was designed to characterize olfactory tissue-specific proteins previously identified with a library of monoclonal antibodies raised against frog olfactory cilia. First, we showed that our olfactory tissue-specific monoclonal antibodies all recognize different molecular forms of the same protein. We named this protein "olfactomedin". We then proceeded to purify olfactomedin and characterize it biochemically and immunohisiochemically. We showed that olfactomedin is produced only in olfactory tissue by sustentacular cells and Bowman's glands and that it is deposited in the lower mucus layer of olfactory neuroepithelium. Next, we extracted mRNA from olfactory tissue and constructed a cDNA library. We obtained partial sequence information of the Nterminus of purified olfactomedin and used these data to design a degenerate oligonucleotide probe for the identification of a fulllength cDNA clone which encodes olfactomedin. This clone was sequenced and found to encode a 448 amino acid protein preceded by a leader peptide of 16 amino acids. Analysis of the sequence showed no homologies with any known protein. Examination of its amino acid sequence by Chou-Fasman analysis in combination with biochemical and immunochemical evidence obtained previously enabled us to construct a model for olfactomedin which identifies this protein as a novel olfactory tissuespecific extracellular matrix protein, which forms the main structural component of the extracellular mucous matrix of olfactory neuroepithelium and which may trigger the growth and differentiation of the dendritic knob and its olfactory cilia that house the olfactory transduction machinery.