The action of arginine vasopressin (AVP) on cytosolic free calcium concentration ([Ca2+]i) was studied at the single-cell level in corticotrophs cultured from pituitary adenoma fragments removed from eight patients with Cushing's disease. AVP evoked distinct [Ca2+]i responses with regard to the tumor origin. In cells from two tumors, AVP consistently evoked a series of characteristic elevations of [Ca2+]i (transient pattern) that depended on Ca2+ entry. In cells from the other tumors, AVP triggered different patterns of [Ca2+]i rise, which consisted of low-amplitude slow monophasic increases at low AVP concentration and a high-amplitude spike increase followed by a sustained plateau (spike-plateau pattern) at higher concentration of AVP. Slow monophasic increases and the spike of spike-plateau responses were due to calcium release from internal stores, whereas the plateau was a consequence of calcium entry. These two patterns (transient vs. spike-plateau) resemble those observed in subpopulations of corticotrophs from healthy rat pituitary glands (Corcuff et al., J. Biol. Chem. 268: 22313-22321, 1993), suggesting that tumorigenesis can lead in pituitary tissues to a selection rather than alteration of AVP [Ca2+]i signals.