In rings of rabbit facial vein (RFV), depletion of sarcoplasmic reticulum (SR) Ca²⁺ by caffeine abolished the subsequent isometric contraction to 25 mM K⁺ physiological salt solution (25K-PSS). However, the associated steady-state increase of smooth muscle intracellular free Ca²⁺ concentration ([Ca²⁺]_i), measured using fura PE3 and cuvette photometry, was not altered. Treatment with the specific SR Ca²⁺ pump inhibitor cyclopiazonic acid (30 µM) after caffeine-induced SR Ca²⁺ depletion restored and greatly augmented the 25K-PSS-induced contraction. This suggests that SR Ca²⁺ depletion leads to a dissociation of K⁺-induced [Ca²⁺]_i increase from contraction that was dependent on Ca²⁺ pump-mediated SR Ca²⁺ uptake. Endothelium removal augmented the 25K-PSS-induced [Ca²⁺]_i increase after caffeine-induced SR Ca²⁺ depletion. However, this was associated with only a small and transient contraction. Exposure of endothelium-denuded RFV to cyclopiazonic acid after caffeine-induced SR Ca²⁺ depletion further amplified the 25K-PSS-induced [Ca²⁺]_i increase, which was associated with a large and sustained contraction. However, the latter [Ca²⁺]_i increase was still higher than in endothelium-intact RFV. This suggests that the endothelium dampens the [Ca²⁺]_i rise associated with K⁺-induced Ca²⁺ influx, but independently of Ca²⁺ pump-mediated SR Ca²⁺ uptake.