A human histamine H1 receptor gene lacking introns was isolated by screening a human genomic library with a bovine histamine H1 receptor probe. The deduced protein of 487 amino acids showed characteristic properties of G-protein-coupled receptors. The coding region was subcloned into the expression vector pSVL (Pharmacia), and the resulting construct transfected into COS-7 cells. Binding studies with [3H]pyrilamine on membranes from transfected cells revealed saturable specific binding with a KD of 1.2 nM and a Bmax of 3400 fmol/mg protein. Binding affinities of histamine and known histamine antagonists were similar to those for histamine H1 receptors in guinea-pig cerebellum. In transfected COS-7 cells, histamine induced inositol phosphate formation, that was inhibitable by pyrilamine.