Differential screening of a cDNA library constructed from human umbilical vein endothelial cells exposed for 1 h to interleukin-1 beta (IL-1 beta) has led to the identification of a novel gene (PTX3) related to pentaxins (C-reactive protein and serum amyloid P component in man), a subclass of acute phase proteins. Sequencing of the full-length cDNA clone and RNase mapping revealed that the PTX3 transcript is 1861 base pairs long and has a unique transcription start site. The predicted protein sequence of 381 amino acids is highly similar to pentaxins in its COOH-terminal half where it also contains a typical 8-amino acid "pentaxin signature" sequence. The NH2-terminal half of PTX3 shows no similarity to any known protein sequence and initiates with a putative signal peptide indicating that PTX3 is secreted. The genome of PTX3 is organized into three exons. Interestingly, the region of homology between PTX3 and pentaxins corresponds to the third PTX3 exon. The PTX3 gene has been localized on human chromosome 3 band q25 by Southern blots of somatic cell hybrids and by in situ hybridization. The PTX3 mRNA is induced in endothelial, hepatic, and fibroblastic cells by IL-1 beta and tumor necrosis factor alpha but not by IL-6 and interferon-gamma. PTX3 may represent a novel marker of inflammatory reactions, particularly those involving the vessel wall.