The creatine concentration of red blood cells was determined in 58 children with congenital acyanotic malformations of the heart at the age of 3 weeks to 3 1/2 years. It was correlated to the severity of the hemodynamic changes, the physical development of the children and number of reticulocytes. The average creatine concentration in the red cells of all patients was 12.8 +/- 4.80 mg/100 ml cells, i.e. twice as high as that of the control group (6.61 +/- 1.19 mg/100 ml cells). Particularly high creatine values were found in children, who died in consequence of their heart disease without previous operation (18.49 +/- 4.25 mg/100 ml cells, n = 11) and those children who had to be operated on as a life-saving measure (17.88 +/- 3.43 mg/100 ml cells, n = 10). The highest creatine concentration was found in a 4 weeks-old infant with hypoplastic left heart syndrome (25.3 mg/100 ml cells). In children with a systolic pressure in the pulmonary artery of greater than 50 torr the creatine concentration was significantly higher than in those with pressures less than 50 torr. Increased creatine values correlated well with the poor physical development and increased reticulocyte numbers of the children. There was no correlation found between capillary pO2 and creatine concentration. It is concluded that the determination of erythrocyte creatine in children with congenital heart disease of the left-right shunt type furnishes additional objective information on the general condition of the organism and its adaptation capacities to hypoxia. It may serve as a valuable diagnostic and prognostic measure.