We compared the effects of transdermal clonidine and oral atenolol on acute exercise performance and on conditioning response to an 8-week program of regular aerobic exercise in young, otherwise healthy subjects with mild hypertension. The study was a double-blind, randomized, parallel-group study with placebo control. Twenty-seven subjects (11 receiving transdermal clonidine, 8 receiving oral atenolol, and 8 receiving placebo) completed the study. Atenolol controlled blood pressure in all 8 subjects, vs 6 of 11 in the transdermal clonidine group and 0 of 8 in the placebo group. Both active drugs lowered systolic blood pressure during exercise. With clonidine treatment, the antihypertensive effect during exercise was smaller and was observed only at low and moderate workloads. Acute exercise performance (subjects receiving drug but still unconditioned) was assessed by endurance time at a constant workload equal to the highest workload completed on a previous 2-minute incremental exercise test. Endurance time was reduced 35% by atenolol but not by transdermal clonidine or placebo. Neither active drug interfered with the progress of the conditioning program, as measured by gradual lengthening of exercise time. However, as assessed by change in oxygen uptake standardized to a heart rate of 170 beats per minute, the improvement in conditioning was twice as great in subjects receiving transdermal clonidine and placebo (+20%, +18%) as it was in those receiving atenolol (+8%). Subjects receiving placebo and transdermal clonidine lost weight; subjects receiving oral atenolol gained weight. The changes in weight were small.