Exposure of porcine carotid artery smooth muscle (PCASM) to histamine was followed by a large reduction in the rate of force generation in response to 40 mM KCl. This was shown to be a manifestation of slow attainment of a steady-state myoplasmic Ca²⁺ concentration ([Ca²⁺]_i). We hypothesized that if net transsarcolemmal Ca²⁺ flux into the depolarized PCASM cells is the same before and after a desensitizing histamine treatment, then the transient attenuation of the increase in [Ca²⁺]_i may be due to accelerated uptake of Ca²⁺ by a partially depleted sarcoplasmic reticulum (SR) acting as a Ca²⁺ sink or superficial buffer barrier. We tested this hypothesis by eliciting responses of "desensitized PCASM" to 40 mM KCl in the presence of cyclopiazonic acid (CPA), an SR Ca²⁺-ATPase inhibitor. Contractions of CPA-treated tissues were attenuated less than those of tissues not treated with CPA, but they were not abolished. CPA-insensitive mechanism(s) dominated the desensitization. We conclude that histamine pretreatment reduced net transsarcolemmal Ca²⁺ flux into PCASM in response to 40 mM KCl.