Differences in caffeine-induced contraction in smooth muscle of resistance vessels from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were investigated by using mesenteric artery preparations. The contraction induced by caffeine (10 mM) was greater in SHRSP preparations, both in the presence and absence of Ca (10 min after Ca removal). Caffeine-induced contraction was gradually decreased by the removal of extracellular Ca. No significant difference was observed in the time course of the decay of the contraction between SHRSP and WKY preparations, and the contraction disappeared when the time in Ca-free solution exceeded 80 min. The contraction induced by high-K-Tyrode’s solution was completely abolished within 10 min after Ca removal, both in SHRSP and WKY preparations. Caffeine-induced contraction could be blocked by procaine or ryanodine. The results suggest that caffeine induces contraction by releasing Ca from sarcoplasmic reticulum, and that the release of Ca is greater in SHRSP vascular smooth muscle. It is also suggested that sarcoplasmic reticulum is leaky for stored Ca when extracellular Ca is removed, and that the rate of leakage does not differ between smooth muscle cells of SHRSP and WKY mesenteric arteries.