The antihypertensive effect of moxonidine X HCl X H2O (MOX) was compared with that of clonidine X HCl (CLON) in a randomized double-blind crossover study in 20 hypertensive outpatients (BP range 154-178/96-108 mmHg). After 2 weeks without antihypertensive medication, either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg. The first treatment period was continued for 2 weeks and, after crossover without a wash-out period, it was followed by the second treatment for a further 2 weeks. Within the first 4 days of administration 0.2-0.4 mg of either agent caused a significant decrease in BP (p less than 0.001) from a mean of 166/100 mmHg to 149/86 mmHg after CLON (approx. -10/-14%), and 163/99 mmHg to 146/84 mmHg after MOX (approx. -10/-15%). No significant difference in the fall in BP or pulse rate was detected between the two drugs. In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity, but on CLON a higher incidence of side effects (p = 0.003) was noted, and after discontinuation of therapy a more rapid rise in BP (systolic BP p less than 0.01, diastolic BP p less than 0.02) was found. 17 patients on CLON complained of side effects, especially tiredness and dry mouth, whilst only 6 patients on MOX were affected (p = 0.003).