Methyldopa (25, 50 and 100 mg/kg, i.p.) was studied for its effect on cardiac arrhythmias and lethality induced by slow intravenous infusion of ouabain in guinea-pigs. Methyldopa increased the dose of ouabain required to elicit the arrhythmic stages and lethality. However, it did not provide any protection in reserpinized guinea-pigs. Methyldopa also inhibited the rate of the ouabain-induced rise in blood pressure and the peak pressor response. Yohimbine significantly antagonized the protective action of methyldopa. It is concluded that the protective action of methyldopa against the arrhythmogenic and lethal effects of ouabain may be due to its action on the indirect neural components of ouabain toxicity, mediated through stimulation of alpha2-adrenoceptors.