In a myocyte freshly isolated from rabbit cerebral artery, the characteristics of Ca2⁢ release by histamine or caffeine were studied by microspectrofluorimetry using a Ca2⁢-binding fluorescent dye, fura-2. Histamine (5 ㄍM) or caffeine (10 mM) induced a phasic rise of cytoplasmic free Ca2⁢ concentration ([Ca2⁢]c) which could occur repetitively with extracellular Ca2⁢ but only once or twice in Ca2⁢-free bathing solution. Also, the treatment with inhibitor of sarcoplasmic reticulum Ca2⁢-ATPase suppressed the rise of [Ca2⁢]c by histamine or caffeine. In Ca2⁢-free bathing solution, short application of caffeine in advance markedly attenuated the effect of histamine, and vice versa. In normal Ca2⁢-containing solution with ryanodine (2 ㄍM), the caffeine-induced rise of [Ca2⁢]c occurred only once and in this condition, the response to histamine was also suppressed. On the other hand, in the presence of ryanodine, histamine could induce repetitive rise of [Ca2⁢]c while the amplitude of peak rise became stepwisely decreased and eventually disappeared. These results suggest that two different Ca2⁢-release mechanisms (caffeine-sensitive and histamine-sensitive) are present in rabbit cerebral artery myocyte and the corresponding pools overlap each other functionally. Increase of [Ca2⁢]c by histamine seems to partially activate ryanodine receptors present in caffeine-sensitive pool.