By equilibrium dialysis of human plasma it has been shown that the binding of pentobarbital and diphenylhydantoin to plasma proteins is decreased in uraemic patients (46 and 74 per cent bound, respectively) compared to healthy volunteers (61 and 88 per cent bound). The degree of binding of pentobarbital was significantly correlated with that of diphenylhydantoin and amobarbital, which suggests similarity of their binding sites. Appreciable proportions of the drugs were found in blood cells both in healthy and uraemic subjects. As expected, the distribution of drugs in whole blood was different in the uraemics from healthy subjects, because of the decreased plasma protein binding and the lowered red cell count in uraemia. Analysis of the data showed that the ratio between the concentrations in blood cells and plasma water in uraemic patients was not significantly different from that in healthy subjects.