A cDNA library of human umbilical vein endothelial cells exposed to fluid shear stress was constructed to search for functional endothelial genes expressed under flow conditions, and cDNAs encoding members of the G protein-coupled receptor (GPCR) family were cloned by a polymerase chain reaction (PCR) method using degenerate oligonucleotide primers. One of the two GPCR clones obtained was edg-1, and the other clone is a novel gene named FEG-1 that encodes a 375-amino acid protein similar to the receptors for both angiotensin II and chemokines. Reverse transcriptase-PCR showed that the FEG-1 and edg-1 mRNA levels in endothelial cells increased markedly in response to fluid flow. This suggests that FEG-1 and edg-1 may be receptor genes that play important roles in the regulation of endothelial function under physiological blood flow conditions.