The pharmacokinetic as well as pharmacodynamic properties of a transdermal clonidine, M-5041T (M) and its safety were compared with those of oral clonidine, Catapres (Nippon Boehringer Ingelheim, Hyogo, Japan). One patch of M containing 6 mg of clonidine was applied on the right chest for 3 days or one tablet of Catapres (.075 mg) was given orally every 12 hours for 3 days in eight healthy subjects. The study was conducted by a crossover design with 14 to 16 days' interval between the cross-over. Blood and urine samples for clonidine concentration were obtained, and blood pressure (BP) was measured for a 168-hour period after application of M and for a 96-hour period after initiation of Catapres therapy. Plasma concentration of clonidine increased gradually after application of M and decreased gradually after removal, whereas this parameter increased rapidly during the absorption phase and decreased rapidly in the elimination phase after each dosage of Catapres. Elimination half-life of clonidine after removal of M was significantly greater than that after the final dosage of Catapres. No significant difference was observed in maximum plasma concentration or area under the plasma concentration-time curve between the two trials. The BP lowering effects of M and Catapres did not differ significantly. Adverse symptoms occurred more frequently during Catapres therapy than during treatment with M. Most of these symptoms were observed when plasma clonidine concentration was relatively higher in each trial. These results suggest that M is effective for the treatment of hypertension with a lower incidence of adverse symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)