Skeletal or smooth muscle alpha-actin isoform is reexpressed in hypertrophied or failing heart in experimental animals, however, it has been unknown whether there is a switching of these genes in the human heart. In this study, we assessed alpha-actin isoform mRNA in biopsied specimens from the left ventricle of patients with dilated cardiomyopathy (DCM). The biopsy was performed in 21 patients (DCM; 16, normal; 5). Skeletal and smooth muscle alpha-actin mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction using a synthetic RNA as internal control. The level of both alpha-actin mRNAs correlated well with the mean cardiomyocyte diameter as an index of cardiac hypertrophy. Further, there was a clear correlation between the expression of skeletal alpha-actin mRNA or smooth muscle alpha-actin mRNA and the ejection fraction. These results suggested that mRNAs for skeletal and smooth muscle alpha-actin isoforms are increased in the hypertrophic and/or failing heart. These mRNAs may be an useful marker for the pathological state of cardiomyopathy.