A brief overview of recent findings of abnormal contractile function of smooth muscle under several selected pathophysiological conditions is presented and related to the dysfunction of the control of cytosolic calcium ion concentration, [Ca2+]. In diabetes mellitus (DM), contractile abnormalities depend on the animal species, vascular segments, mode of the induction of DM, and the period after the induction of DM. The abnormal contractile responses are frequently related to altered Ca2+, membrane transduction and the production and action of intracellular second messengers. The hypertensitive and/or hyperreactive contractile responses of airway smooth muscle in asthma inflammation represent a complex chronic consequence of actions of many cells and mediators. Chronic asthmatic disease seems to be associated with altered Ca2+ handling via changes in gene coding for receptors, enzymes and regulatory proteins, thus contributing to abnormal responsiveness and cell growth. Similarly, changes of contractile function of vascular smooth muscle commonly observed in chronic hypertension have long been recognized to be intimately associated with abnormal handling of Ca2+ at the level of subcellular membranes, isolated cells and intact vascular tissues. However, the subcellular sites of membrane abnormalities remain disputable.