Inositol 1,4,5-trisphosphate (IP3) caused a contraction in skinned single smooth muscle cells from the guinea-pig taenia coli. The contractile response to IP3 was rapid (half time less than 5 s), concentration-dependent (0.01-10 microM, EC50; 0.1 microM) and also depended on the concentration of Ca2+ during preloading. IP3 induced a rapid 45Ca2+ release from the skinned single cells which were preloaded with 10(-6) M Ca2+. The contractile response caused by IP3 was not enhanced by simultaneous application of caffeine (25 mM). The inhibitory effect of procaine on IP3-induced contraction was less than that on caffeine-induced contraction. These results suggest that IP3 also plays an important role in the contractile response in smooth muscle cells from guinea-pig taenia coli and that the mechanism of Ca2+ release from intracellular storage sites by IP3 is different from that by caffeine.