We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified.