Whether alcohol-induced heart failure is caused by a direct toxic effect of ethanol, metabolites, or whether it is a secondary result of neurohumoral, hormonal, or nutritional factors is not clear, To address this question a Langendorff retrograde coronary perfusion model of rat heart was used to study the effect of 0.5% (v/v) ethanol (n = 7) and 0.5 mM acetaldehyde (n = 9) on left ventricular expression of ANP, BNP, p53, p21, TNF-alpha, bax, bcl-2 as well as on DNA-fragmentation. Ethanol infusion of 150 min duration significantly induced both ANP and p21 mRNA expression of ventricular myocardium compared with hearts infused with vehicle (n = 8), Acetaldehyde did not exert any significant effects on any of the parameters studied, although the mean expression of TNF-alpha tended to be lower in the acetaldehyde-treated hearts than in control hearts. No evidence of increased DNA-fragmentation was found in ethanol or acetaldehyde treated groups. We conclude that ethanol per se is capable of inducing genes associated with hypertrophy and impaired function of the heart whereas a significant apoptosis is not involved in the initial phase of alcohol-induced cardiac injury.