Serum carnitine is an essential cofactor for the transport of free fatty acids into the mitochondria. We determined the free and the total serum carnitine in 99 healthy blood donors and 58 patients with different forms of heart muscle disease. Thirty patients had dilated (DCM), 10 hypertrophic (HCM) and 8 alcoholic (ACM) cardiomyopathy and 10 patients had congestive heart failure of different etiology than cardiomyopathy (CHF). Free and total serum carnitine were determined by an enzymatic-spectrophotometric assay according to Pearson. Mean values for free and total serum carnitine were as follows: 47 and 74 mumol/l in controls (C; blood donors), 74 (P less than 0.01 vs. C) and 83 mumol/l in DCM, 66 (P less than 0.01 vs. C) and 89 mumol/l in HCM, 85 (P less than 0.01 vs. C) and 104 mumol/l (P less than 0.05 vs. C) in ACM and 86 (P less than 0.01 vs. C) and 129 mumol/l (P less than 0.01 vs. C) in CHF. Ten patients died during the mean observation time of 13 months, 8 patients with DCM and 2 with CHF; 9 of these 10 patients had initially a markedly increased serum carnitine. Patients with DCM were divided into two groups with normal (n = 15; 25-68 mumol/l) and increased (n = 15; greater than 68 mumol/l) free serum carnitine. Patients with increased serum carnitine showed a significantly higher mortality rate (47%) than patients with normal serum carnitine. It is concluded that free and total serum carnitine are elevated in patients with congestive heart failure, dilated and hypertrophic cardiomyopathy. The etiology of this carnitine metabolism disturbance is unclear but it is probably due to a secondary phenomenon in patients with congestive heart failure or primary myocardial hypertrophy. An increased serum carnitine is a poor prognostic sign in patients with dilated cardiomyopathy.