Brinerdin (Sandoz), a combination of a diuretic (clopamide 5 mg), a vasodilator (dihydro-ergocristine 0.5 mg) and reserpine (0.1 mg)(CDR) was compared with methyldopa (MD) plus hydrochlorothiazide (HCT) for antihypertensive effect, adverse reactions, compliance and patient preference in an open cross-over trial. Eighteen patients completed both arms of the trial and 5 patients who completed the CDR arm were withdrawn while on the MD arm because of adverse effects in 4 and poor control in 1. On HCT 50 mg daily the mean baseline systolic blood pressure was 163.9+/-16.3 mmHg and the diastolic blood pressure was 105.9+/-6.7 mmHg. On CDR these were reduced to systolic blood pressure 140.3+/-15.1 mmHg and diastolic blood pressure 87.8+/-9.3 mmHg. On MD+ HCT the systolic blood pressure was reduced to 138.5+/-16.9 mmHg and the diastolic blood pressure to 88.9+/-10.3 mmHg. The differences between the two treatment periods in systolic blood pressure (1.8 mmHg; 95% confidence interval (CI)-4.1+ 7.7 mmHg) and diastolic blood pressure (1.1 mmHg; 95% CI-4.6+ 2.4 mmHg) were not significant with P values of 0.6 and 0.7 respectively. Compliance was 98.2% for CDR and 94.7% for MD+ HCT (P= 0.02). Unusual sleepiness occurred more frequently in the MD arm (P less than 0.01). Thirteen patients chose to continue on CDR, 2 on MD+ HCT and 3 had no preference (P= 0.005). CDR is similar in antihypertensive effect to MD+ HCT but is better tolerated with fewer withdrawals, fewer adverse effects, better compliance and has more patients electing to continue taking it.