Ten patients with essential hypertension were treated orally with clonidine, and the dose was titrated until the diastolic pressure fell below 90 mm Hg or at least 10 mm Hg below baseline, or until a maximum dose of clonidine of 1.2 mg/day was reached. After at least 2 wk on a constant dose of clonidine, the patients were hospitalized and blood pressure and plasma clonidine concentrations were measured by a highly specific and sensitive gas chromatographic, electron-capture method (sensitivity as low as 0.1 ng clonidine/ml). There was good correlation between daily clonidine dose and plasma clonidine concentration. The average blood pressure reduction during 12 hr after clonidine correlated poorly with steady-state plasma levels of clonidine, but when the individual maximum decrease in mean blood pressure was paired with the corresponding peak plasma concentration of clonidine, the correlation was strong.