Large fluctuations of blood pressure are commonly experienced by hypertensive, chronic hemodialysis patients. Many patients hold anti-hypertensive medication immediately prior to dialysis to prevent intradialytic hypotension. Weekly dosing of continuously released antihypertensive agents may result in better blood pressure control than conventional daily dosing. To evaluate the effect of weekly transdermal clonidine on this problem, we compared intra- and interdialytic blood pressure control and side effects during six weeks of transdermal clonidine monotherapy and six weeks of conventional oral antihypertensive treatment in nine stable chronic hemodialysis patients. Since transdermal clonidine is recommended for mild to moderately severe hypertension and since clonidine is excreted by the kidneys and removed by hemodialysis, we also evaluated blood pressure control and clonidine levels while utilizing high-dose transdermal clonidine, up to 0.12 mg per week. Intradialytic blood pressure was monitored twice weekly during the weeks 3-6 of transdermal clonidine and conventional therapy. Twenty-four hour blood pressure was monitored weeks 3 and 6 of each study phase. Plasma clonidine levels were measured by HPLC in 11 patients. Transdermal clonidine monotherapy failed to adequately control blood pressure in 6 of 21 chronic dialysis patients with moderate to severe hypertension. No significant difference in intra- or interdialytic blood pressure control or side effects (including dry mouth or thirst) was found comparing conventional to transdermal clonidine therapy. While not statistically different, heart rate was lower during transdermal clonidine therapy compared to conventional therapy, especially at very high doses. Despite a mean hemodialysis clearance of clonidine of 59.2 +/- 7.8 ml/min, clonidine levels remained therapeutic beyond one week.(ABSTRACT TRUNCATED AT 250 WORDS)