The calcium dependence of potassium chloride-, prostaglandin F2 alpha (PGF2 alpha)-, and histamine-induced contractions of human chorionic vasculature segments was investigated. In physiologic buffer that contained 1.5 mM calcium chloride, 60 mM potassium chloride induced a rapid and sustained contraction of the vasculature. Potassium chloride-induced contractions were completely inhibited by the calcium channel blockers diltiazem and nifedipine or by excluding Ca2+ from the medium. Histamine (100 microM) induced a rapid increase in vascular tension in physiologic buffer which rapidly faded or desensitized after maximal tension was obtained. The maximal contractile responses to histamine were reduced approximately 50% by diltiazem and nifedipine in physiologic buffer or by suspension in calcium-free medium (OCaPB). Pretreatment of vessels with 20 mM caffeine in OCaPB completely abolished histamine-dependent contractile responses. Prostaglandin F2 alpha (100 nM)-induced increases in vascular tension developed slowly but remained maximal for at least 40 minutes. Contractile responses to PGF2 alpha were reduced 50% to 65% by diltiazem and nifedipine in physiologic buffer or by suspension in OCaPB. Caffeine pretreatment failed to alter the contractile response to PGF2 alpha in OCaPB. The differences in responsiveness of potassium chloride, histamine, and PGF2 alpha under the various conditions used suggest that these agents act by different mechanisms to elicit contractions in chorionic vessels. The potential roles of PGF2 alpha, histamine, and calcium channel blockers in modulating the fetoplacental circulation is discussed.