Five patients with moderate hypertension were given placebo and at least 3 single oral doses (25, 50, 75, 100, or 150 mg) of metoprolol as well as multiple doses at at least 2 dose levels (25, 50, or 100 mg thrice daily). Blood pressure, pulse rate at rest, plasma renin activity, and drug plasma concentration were intensively monitored during 7.5 hr after each dose. Pulse rate, systolic blood pressure, and plasma renin activity decreased after the single oral doses, but diastolic blood pressure did not decrease consistently. The correlation coefficients between percentage decrease in systolic blood pressure and pulse rate and total plasma concentrations were higher individually than in the group. The corresponding regression equations were different between individuals and for systolic blood pressure there was a 700% difference in regression coefficients. The acute changes in diastolic blood pressure and plasma renin activity were not related to metoprolol plasma concentrations. The decrease in systolic blood pressure and pulse rate on multiple doses could not be predicted from the response after single doses.