Arteries that have developed myogenic tone (MT) are in a markedly different physiological state compared to those that have not, with higher cytosolic [Ca²⁺], and altered activity of several signal transduction pathways. In this study, we sought to determine whether ₁-adrenoceptor induced Ca²⁺signaling is different in pressurized arteries that have spontaneously developed MT (the presumptive physiological state), compared to those that have not (a common experimental state). Before MT: At 32°C and intraluminal pressure of 70 mm Hg, cytoplasmic [Ca²⁺] was steady in most smooth muscle cells (SMC). In a minority of cells however, (34%) at least one propagating Ca²⁺ wave occurred. ₁-adrenoceptor activation (phenylephrine, PE, 0.1 to 10.0 µM) caused strong vasoconstriction and markedly increased the frequency of Ca²⁺ waves (in virtually all cells). However, when cytosolic [Ca²⁺] was elevated experimentally in these arteries ([K⁺], 20 mM), PE failed to elicit Ca²⁺ waves, although it did elevate [Ca²⁺] (F/F0) further and cause further vasoconstriction. After MT: During development of MT, the cytosolic [Ca²⁺] (F/F0) in individual SMC increased, Ca²⁺ waves disappeared (from SMC that had them), and small Ca²⁺ ripples (frequency; ~ 0.05 Hz) appeared in ~ 13% of cells. PE elicited only spatially uniform increases in [Ca²⁺], and smaller change in diameter (than in absence of MT). Nevertheless, when cytosolic [Ca²⁺] and MT were decreased by nifedipine (1.0 µM), PE did elicit Ca²⁺ waves. Thus, ₁-adrenoceptor mediated Ca²⁺ signaling is markedly different in arteries with and without MT, perhaps due to the elevated [Ca²⁺] and may have a different molecular basis. ₁-adrenoceptor induced vasoconstriction may be supported either by Ca²⁺ waves or by steady elevation of cytoplasmic [Ca²⁺], depending on the amount of MT.