Heart failure is associated with a decreased variability in circadian systolic blood pressure. ACE inhibitors have been shown to be beneficial in CHF. However, the effect of the magnitude of the dose of ACE inhibitor on blood pressure variability has not been reported. The objective of this sub-study of the ATLAS trial was to determine if there was a difference in effect on systolic blood pressure variability of two doses (35 mg, 'high' and, 5 mg, 'low') of the ACE inhibitor, lisinopril, in patients with heart failure (class Ii-IV; NYHA), Criteria for inclusion were: symptomatic heart failure (dass Ii-IV; NYHA), left ventricular ejection fraction less than or equal to 30%, and 2 months of conventional therapy with diuretics with, or without, digoxin. Twenty-four hour ambulatory blood pressure was recorded prior to randomization and after peak titration (4 weeks) of the study drug for analysis of variability of systolic blood pressure variability. The high dose of lisinopril was associated with greater variability of 24 h systolic blood pressure as noted by inspection of the 24 h recordings or calculation of the blood pressure variability index (P < 0.05). The greater variability in SEP was not associated with a difference in mean 24h arterial blood pressure. Conclusions Variation in circadian systolic blood pressure is useful in reflecting the influence of the magnitude of dose of the ACE inhibitor lisinopril on the pharmacodynamics of patients with heart failure. Blood Press Monit 6:81-84 (C) 2001 Lippicott Williams & Wilkins.