Calcium channel blockers and central alpha-agonists are among the classes of antihypertensive drugs that yield the most favorable overall effects on risk factors for hypertension-related end-organ damage. An open-label prospective trial in 42 patients with a mean baseline blood pressure of 144/102 mm Hg sought to assess the usefulness of adjunctive treatment with transdermal clonidine (0.1 to 0.3 mg/day) in patients responding inadequately to nifedipine--gastrointestinal therapeutic system (GITS) (30 to 60 mg/day) monotherapy. Thirty-nine patients who failed to reach the goal of a seated mean diastolic blood pressure of < 90 mm Hg when treated only with once-a-day nifedipine-GITS entered a transdermal clonidine (once a week) titration phase followed by an 8-week maintenance course of the two drugs combined. The 35 patients completing this last phase responded with a mean seated diastolic blood pressure of 127/87 mm Hg. Only six patients required the highest dose of clonidine for control. A 97% compliance rate with the transdermal medication contrasted with a compliance rate of only 73% for the oral nifedipine. Two of three patients who had contact dermatitis after wearing a transdermal clonidine patch withdrew from the trial prematurely; other minor side effects required no interruption of therapy. The nifedipine-clonidine combination not only achieved blood pressure control in these patients but may prove advantageous in combining the protective effects of the two agents against complications of the hypertensive syndrome.