The influence of short-time incubation in hyperosmolar sugar solutions on the contractile responses of vascular smooth muscle was examined using isolated rings of rabbit ear arteries. Hyperosmotic mannitol (50 mM) did not alter the resting tone. Bolus administration of 0.1 mM Ca++ along with norepinephrine to vessels incubated in Ca++-free medium induced biphasic responses. Potassium chloride (KCl 30 mM) produced tonic contractile responses. Administration of hyperosmotic mannitol (50 mM) for 5 min significantly inhibited contractile responses to norepinephrine and KCl. Pretreatment with hyperosmotic mannitol (50 mM) for 30 min significantly inhibited cumulative dose-response curves to Ca++ in 60 mM KCl depolarizing solution. Exposure to a K+-free medium for 2 to 3 hr induced contractions even in the presence of phentolamine (2.65 X 10(-6) M) and addition of hyperosmotic mannitol (50 mM) further enhanced these contractions instead of inhibiting them in these vessels. Moreover, hyperosmotic mannitol (50 mM), sucrose (50 mM) and raffinose (50 mM) also induced contractions in arterial muscles incubated in K+-free medium at resting tension. Hypertonic mannitol (50 mM) enhanced contractile responses to ouabain in muscles which had been stored at 2 degrees C for 10 days but inhibited ouabain-induced responses in fresh arteries even in the presence of phentolamine. These experiments indicate that hyperosmolarity inhibits vascular reactivity to some agonists possibly by inhibiting excitation-contraction coupling; however, under certain conditions, i.e. after blockade of the sodium pump by K+-free solution or by ouabain, hyperosmolarity may actually induce vascular contractions.