The objective of this study was to assess the influence of the ACE gene insertion (I)/deletion (D) polymorphism on plasma ACE activity; blood pressure; and risk of myocardial infarction, ischemic heart disease, and ischemic cerebrovascular disease by comparing small and large studies. The meta-analyses are based on a literature search of MEDLINE up until April 1998 and assessment of bibliographies of published studies and reviews. Forty-six studies were selected, including a total of 32 715 white individuals. Plasma ACE activity was increased 40% and 71% for ID and DD versus II in small studies and 21% and 48% in large studies (small versus large: P<0.001 and P<0.001). Blood pressure was not influenced by genotype. Risk of myocardial infarction and ischemic heart disease was increased by 47% and 29%, respectively, for DD versus ID and II genotypes in small studies but not in large studies (small versus large: P<0.001 for risk of myocardial infarction and P=0.01 for risk of ischemic heart disease). Risk of ischemic cerebrovascular disease was not increased either in the small or in the largest study. In conclusion, the ACE gene polymorphism affects plasma ACE activity but not blood pressure and is not associated with increased risk of myocardial infarction, ischemic heart disease, or ischemic cerebrovascular disease in the largest studies.