1. The actions of phenylephrine (0.1-100 mumol l-1) and methoxamine (0.1-100 mumol l-1) were compared with that of adrenaline (0.01-10 mumol l-1) using the single sucrose gap method and mechanical recording in the guinea-pig taenia caeci. Drugs were applied for variable periods of time. 2. The characteristics of the inhibitory effects of alpha-adrenoceptor agonists were the same when exposure time did not exceed 5 min. When the exposure was prolonged, in contrast to the sustained effects of adrenaline (0.1-3 mumol l-1), phenylephrine and methoxamine (1-10 mumol l-1) produced a transient inhibitory action. 3. During the delayed recovery phase of phenylephrine, adrenaline preserved its ability to suppress the spontaneous electrical and mechanical activities of the taenia both when phenylephrine was replaced by adrenaline or when adrenaline was applied in addition to phenylephrine. All the above effects were found in untreated preparations, as well as during blockade of muscarinic cholinoceptors by atropine (1.4 mumol l-1), beta-adrenoceptors by propranolol (3 mumol l-1) and release of endogenous catecholamines by guanethidine (2.5 mumol l-1). 4. In the presence of phorbol 12,13-dibutyrate adrenaline ceased to be effective, while the inhibitory action of phenylephrine was converted to a contraction. 5. In calcium-free conditions in the presence of EGTA (0.4 mmol l-1) the initial hyperpolarization induced by adrenaline and phenylephrine was significantly reduced and with repeated applications of the agonists the inhibitory response disappeared. Similar results were obtained using tissues treated with nifedipine (1 and 10 mumol l-1). When caffeine (30mmolI 1) was present in the calciumfree solution the alpha-agonists studied were unable to produce any membrane potential changes. 6. The present results imply that the inhibitory effect of alpha-adrenoceptor agonists is mediated by the opening of potassium channels, which are activated by calcium derived from an intercellular source supplied from the extracellular space via a nifedipine-sensitive mechanism.