Enalapril in single doses of 5 and 10 mg and atenolol in a single dose of 50 mg were given to 16 hypertensive patients on long-term treatment with bendrofluazide, 5 mg daily, in a double-blind randomized crossover placebo controlled study. Both doses of enalapril and atenolol produced similar effects on blood pressure. The mean maximal reduction in blood pressure from baseline with all three active treatments was approximately 32/18 mmHg both supine and standing and occurred on average at 6 h after tablet ingestion. Both supine and standing heart rate fell significantly after atenolol, but no significant change occurred after enalapril. This study establishes that 5 mg enalapril is the maximal starting dose that need be used in hypertensive patients already on diuretic treatment. Even this dose may be hazardous in some patients. The study also serves to emphasize that such combination-therapy studies should be carried out at an early stage in drug development, prior to widespread prescription to patients, in order to avoid unnecessary overdosage with new agents.