Heart fragments obtained from human right atrium contain 1.5 +/- 0.2 micrograms of histamine per gram of wet tissue. Human heart spontaneously synthesizes significant amounts of PGI2, PGF2 alpha, PGE2 and TxA2. The Ca2+ ionophore A 23187 (0.5-3 micrograms/ml) dose-dependently induces histamine release and prostanoid production. Histamine (0.5-1 micrograms/kg/min) infusion in 10 normal donors produced an increase in heart rate and a significant depression of the ST segment. Selective H1 receptor stimulation in patients undergoing cardiac catheterization resulted in a decrease of the mean aortic pressure and of coronary vascular resistance.