The presence of the inducible nitric oxide synthase (iNOS) has previously been reported in heart and skeletal muscle of patients with chronic heart failure, where it is thought to be involved in the pathogenesis of dilated cardiomyopathy or of exercise intolerance observed in patients with chronic heart failure. To identify the iNOS of these human tissues the cDNA sequence was determined using reverse transcription polymerase chain reaction (RT-PCR). The deduced amino acid sequence of human heart and skeletal muscle shows a 99% identity between each other. The amino acid sequence was distinct from the constitutively expressed nitric oxide synthases. A 98% identity at the protein level was detected to rat vascular smooth muscle iNOS, whereas the homology to human hepatocyte iNOS was only 79%. The cofactor binding sites in the reported iNOS from human heart and skeletal muscle are highly conserved. The iNOS sequence described in this report is the first one isolated directly from human tissue expressing iNOS in the circumstances of chronic heart failure.