The properties of contractile elements and intracellular Ca2+ storage sites of pregnant human myometrium were studied by recording the mechanical responses in skinned (saponin-treated and membrane-permeable) fibres. Calmodulin increased the amplitude of contractions induced by Ca2+ and the Ca2+ sensitivity for contractile elements in small myometrium strips, but PGF2 alpha, PGE2, oxytocin, or cyclic AMP failed to produce similar effects. After accumulation of Ca2+ in intracellular Ca2+ storage sites, 10 mumol/l PGF2 alpha, 10 mumol/l PGE2, 30 mmol/l caffeine, and 20 mumol/l InsP3 (inositol-trisphosphate) produced contractions by releasing Ca2+ from storage sites. However, 20 nmol/l oxytocin had no effects under the same conditions. The InsP3 sensitive Ca2+ store was much larger than those of PGs or caffeine. These results suggest that pregnant human myometrium contracts with low Ca2+ by a calmodulin sensitive system. The data also indicate that direct application of PGF2 alpha, or PGE2 into the cells discharges Ca2+ from Ca2+ storage sites and that oxytocin extricates Ca2+ via a pathway involving InsP3 by activation of phosphoinositide turnover. We suggest that these agents induce added contractile responses due to a Ca2+ release mechanism from store sites in addition to the influx of Ca2+ from the extracellular space.