Superficial sarcoplasmic reticulum (SR) regulates smooth muscle force development directly by Ca²⁺ release and removal to and from the cytoplasm (Somlyo and Somlyo. J Cardiovasc Pharmacol 8, Suppl 8: S42-S47, 1986) by buffering Ca²⁺ influx and contributing to Ca²⁺ extrusion (Mueller and van Breemen. Nature 281: 682-683, 1979) and indirectly by releasing Ca²⁺ near Ca²⁺-activated K⁺ channels (K_Ca) to hyperpolarize the plasma membrane (Bolton and Imaizumi. Cell Calcium 20: 141-152, 1996 and Nelson et al. Science 270: 633-637, 1995). In the rabbit basilar artery, relative contributions of direct effects and those mediated through activation of K_Ca were evaluated by measuring force and intracellular Ca²⁺ concentration ([Ca²⁺]_i) in response to the SR-depleting agents thapsigargin and ryanodine and the large conductance K_Ca (BK_Ca) blockers iberiotoxin (IbTX) and tetraethylammonium ion (TEA). A large contraction was observed in response to K_Ca blockade with either 3 mM TEA or 100 nM IbTX and also after addition of 10 µM ryanodine or 2 µM thapsigargin. When K_Ca was blocked first with TEA or IbTX, subsequent addition of thapsigargin or ryanodine also increased force. Measurements of fura 2 fluorescence showed parallel increases in [Ca²⁺]_i in response to sequential blockade of sarco(endo)plasmic reticulum Ca²⁺-ATPase and K_Ca regardless of the order of application. It appears that a significant fraction of K_Ca remains activated in the absence of SR function and that SR contributes to relaxation after blockade of K_Ca. We found that depletion of SR before stimulating Ca²⁺ influx through voltage-gated Ca²⁺ channels markedly reduced force development rate and that thapsigargin abolished this effect. We conclude that the SR of rabbit cerebral arteries modulates constriction by direct and indirect mechanisms.