Inflammation is an important factor in the development and progression of atherosclerosis. Observational studies have suggested that renin-angiotensin system inhibition might lower C-reactive protein (CRP). The aim of this study was to test the hypothesis that angiotensin-converting enzyme inhibition with fosinopril would reduce inflammation in a placebo-controlled trial involving 621 subjects. CRP was determined using a high-sensitivity assay at baseline and after 3 months of fosinopril treatment. The median CRP level at baseline was 1.38 mg/dl (interquartile range 0.64 to 2.86) and did not significantly differ between treatment groups. CRP levels at baseline were significantly associated with future cardiovascular events, even after adjustment for age and gender (odds ratio 1.76, 95% confidence interval 1.16 to 2.67, p = 0.008). Fosinopril treatment during 3 months did not result in a significantly higher reduction of CRP levels compared with placebo (difference -0.11, p = 0.20). Exploratory analysis suggested an interaction between gender and fosinopril treatment on CRP reduction (p = 0.07). Male gender was associated with a significantly larger reduction in CRP compared to female gender. In conclusion, contrary to previous observational studies, no effect of angiotensin-converting enzyme inhibition on CRP levels was found. (C) 2008 Elsevier Inc. All rights reserved.