The binding of carbromal and its metabolites bromoethylbutyramide and ethylbutyrylurea to human plasma proteins was investigated in vitro by use of Sephadex-gelfiltration, equilibrium dialysis and ultrafiltration. No differences appeared in the binding characteristics of human plasma and of human albumine. In a concentration range between 3.10-8 and 1.5.10-6 moles/ml about 40% of the carbromal, and in a concentration range between 3.10-8 and 1.10-5 moles/ml about 30% of the bromoethylbutyramide are bound to plasma proteins. Proteinbinding of ethylbutyrylurea was found to be less than 5%. The binding constants, Ka, to human albumine and the binding energies deltaF 0 were found to be in the range of 0.5--1.2.10(3) L/Mol and 1.7--4.4 kcal/Mol, respectively. Protein binding of carbromal, bromoethylbutyramide, their chlorinated analgous compounds, chloroethylbutyrylurea and chloroethylbutyramide, and of ethylbutyrylurea is strongly correlated to the partition coefficients of these compounds between n-octanol and water, indicating that the intensity of proteinbinding depends on the hydrophobic character of the substances tested.