Agonists and antagonists of histamine were used to characterize the stimulation of inositol phosphates formation and elevation of intracellular Ca2+by histamine in cultured non-pigmented epithelial (NPE) cells from human ciliary body. Agonists specific for the H1histamine receptor subtype were 20-to 200-fold more potent than the H2-specific agonists tested, and 5–16% as potent as histamine in inositol phosphates stimulation. An H1antagonist was 10,000-fold more potent than an H2antagonist in blocking histamine stimulation of inositol phosphates. H1agonists also mimicked and H1antagonists inhibited the elevation of intracellular Ca2+by histamine. The first phase of the Ca2+response to histamine was largely independent of extracellular Ca2+while the second phase required extracellular Ca2+. Dose-response curves for histamine elevation of intracellular Ca2+(EC50= 10μM, maximum at 100μM) and inositol phosphates (EC50= 2μM, maximum at 100μM) were similar. These data support the characterization of the NPE histamine receptor as an H1receptor linked to elevation of inositol phosphates and intracellular Ca2+.