Inflammatory cytokines have been shown to have many cardiotoxic effects and to be activated in patients who have had a myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors have been shown to have multiple beneficial effects after MI, but until now, their effects on cardiac cytokine expression were unknown. It was hypothesized that ACE inhibitors reduce cardiac cytokine expression and that this is associated with improved cardiac remodeling and hemodynamics. Rats had an MI created by coronary artery ligation and ACE inhibitors were started either early (day 1) or late (day 25) after MI and followed for a total of 28 days after MI. In the early-post-MI group, quinapril improved cardiac hemodynamics, improved ventricular remodeling, and prevented the increase in the expression of several cardiac cytokines (interleukin-1beta and -6) and reduced the cardiac expression of other cytokines (tumor necrosis factor-alpha and interleukin-5). The late introduction of quinapril (for 3 days) resulted in similar beneficial hemodynamic effects, and reductions in cardiac cytokines but did not result in improved cardiac remodeling. Thus, following MI, ACE inhibitors reduce cardiac cytokine expression both chronically and subacutely, an effect that may contribute to their beneficial effects after MI.