The objective of this study was to assess individual responses to antihypertensive treatment by N-of-1 trials using blood pressure self-monitoring in 79 patients of both sexes referred to a hypertension clinic. Thirty-five patients who remained untreated (study 1) and 44 N-of-1 trial participants (study 2) were consecutively selected if their clinic blood pressure was between 160/95 and 220/115 mm Hg and there were no hypertensive complications. Blood pressure was measured daily at home for 21 days (three consecutive measures, morning and evening). Each N-of-1 trial was a single-blind treatment consisting of two successive 10-day treatment pairs, each pair comprising 5 days of placebo followed by 5 days of 20 mg enalapril once daily in the morning. Study 1 showed no significant blood pressure regression toward the mean over 20 days and justified the choice of 5-day treatment periods in study 2. In study 2, blood pressure fell significantly 12 hours after the first administration of enalapril and rose within 24 hours of the end of the 5-day active treatment period. Using evening blood pressure values (12 hours after enalapril intake) from the first treatment pair, 33 patients were classified as responders (diastolic blood pressure fall greater or equal to 6 mm Hg). In 16 of these 33 patients, the fall in blood pressure above 6 mm Hg was not maintained in the morning, 24 hours after drug intake. Response reproducibility was tested by comparison with the second treatment pair: the observed agreement was only 0.71 (chance-corrected agreement: 0.34) when defined according to both evening and morning values. N-of-1 trial methodology can be useful for decision making in the care of individual patients. It can be based on the use of home blood pressure determinations, provided that there are at least 30 readings in each 5-day trial period. The individual agreement between the antihypertensive responses to two successive enalapril treatment periods is only moderate and is not sufficient to justify using this design for performing in individual patients randomized comparison of an angiotensin-converting enzyme inhibitor and another antihypertensive drug. (Hypertension. 1995;25:294-301.)