1. To explore roles of intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle, we examined the effects of ryanodine, a fixer of ryanodine receptor-Ca(2+) channels to an open state, and thapsigargin, a selective inhibitor of the Ca(2+) pump in the intracellular stores, on smooth muscle contraction in the presence and absence of extracellular Ca(2+) in guinea-pig taenia caeci. 2. In Ca(2+) -free solution, contractions induced by 0.1 mmol/L carbachol and 0.1 mmol/L histamine were reduced to approximately 65% of control by either 1 micro mol/L thapsigargin or 10 micro mol/L ryanodine. In contrast, caffeine-induced contraction was reduced to approximately 40% of control by ryanodine, but was not affected by thapsigargin. 3. In the presence of extracellular Ca(2+), thapsigargin slowly induced a large and sustained contraction. In contrast, ryanodine did not induce an apparent contraction, but increased the sensitivity of contractile responses to receptor agonists (carbachol, AHR-602 and histamine) or depolarizing high K(+) with no changes in the maximal contraction. 4. These results suggest that there are pharmacological and physiological differences between ryanodine- and thapsigargin-sensitive intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle, which may be responsible for their differential effects on the Ca(2+) -influx pathway.