Inositol 1,4,5-trisphosphate (InsP(3)), an intracellular messenger, induces Ca2+ release in various types of cells, particularly smooth muscle cells. Its role in skeletal muscle, however, is controversial. The present study shows that the application of InsP(3) to rat slow- and fast-twitch saponin-skinned fibres induced contractile responses that were not related to an effect of InsP(3) on the properties of the contractile proteins. The amplitude of the contractures was dependent upon the Ca2+-loading period, and was larger in slow- than in East-twitch muscle. In both types of skeletal muscle, these responses, unlike caffeine contractures, were nor inhibited by ryanodine (100 mu M), but were abolished by heparin (20 mu g.ml(-1)), In soleus muscle, the concentration of heparin required to inhibit the response by 50% (IC50) was 5.7 mu g.ml(-1), a similar value to that obtained previously in smooth muscle. Furthermore, the results show that in slow-twitch muscle, the InsP(3) contractures have a "bell-shaped" dependency on the intracellular Ca2+ concentration. These results show that InsP(3) receptors should be present in skeletal muscle. Thus, it is possible that InsP(3) participates in the regulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle, particularly in slow-twitch fibres.