Cyclopiazonic acid (53 or 159 nmol/min) or ryanodine (53 or 530 nmol/min) was applied to perfused rat mesenteric artery contracted with 40 mM K+ and 0.1 mM Ca2+. Both agents transiently elevated the perfusion pressure. The transient pressor response to caffeine observed after ryanodine was depressed more than after cyclopiazonic acid. This suggests that ryanodine increased the constriction through acceleration of Ca2+ release while cyclopiazonic acid increased it by inhibiting Ca2+ uptake into Ca2+ stores. In the continued presence of ryanodine, the next depolarization-dependent constriction was greatly depressed, suggesting that Ca(2+)-induced Ca2+ release was involved in the constriction.