1 Fresh rat aortic rings were incubated in HEPES-buffered salt solutions. Extracellular Ca24 stimulated the production of prostacyclin (PGI2), as determined by radioimmunoassay of its stable hydrolysis product 6-oxo-prostaglandin F,. This action of Ca24 was modified by H4 over the pH range 8.0-6.5. Stimulation by calcium ionophore A23187 was not pH-dependent.2 In parallel incubations of aortic rings with 4 Ca2", followed by washing in the presence of La3, tissue uptake of 45Ca2" increased progressively as extracellular pH was increased from 6.5-8.0. Over this range intracellular pH, estimated by the distribution of ['4CJ-dimethadione, varied from 5.9-7.4.3 Stimulation by Ca24 of PGO2 synthesis was concentration-dependent over the range 0.7-20 mm. The maximum effect was an increase of approx. 4 fold. 4 Nifedipine, but not verapamil or diltiazem, inhibited Ca24-stimulated PGI2 synthesis. A dihydropyridine compound that activates voltage-dependent Ca24 channels, Bay K 8644, did not increase PGI2 synthesis. 5 8-(N, N-diethylamino)-octyl-3,4,5 timethoxybenzoate (TMB-8), an antagonist of intracellular Ca24 mobilisation, inhibited basal and Ca24-stimulated PGO2 synthesis to a similar extent. 6 A solution containing 40 mM K4 reduced Ca24-stimulated PGI2 production. Mg24 stimulated PGI2 synthesis in a pH-dependent manner but was less potent than Ca2 . Other divalent cations (Mn24, Ba24 and Sr`9), and La34 had little or no effect on basal or Ca2+-stimulated PGI2 synthesis.