A polarographic technique has been used to study the oxygen uptake of rat brain homogenates incubated with metabolites known to accumulate in uraemia and hepatic coma. In general, results with individual metabolites were in agreement with those previously obtained with brain slices using the Warburg technique. Inhibition was induced at higher concentrations with urea, creatine, indoxysulphate, guanidine, dimethylamine hydrochloride, ammonium chloride, taurocholate, glycodeoxycholate, sodium deoxycholate, skalote and indole. Serum and ultrafiltrate from drowsy uraemic patients also caused inhibition, and this was reversed by renal dialysis. Similarly serum and ultrafiltrate from patients in hepatic coma inhibited oxygen uptake but in this instance reversal of the inhibition was not demonstrated following exchange blood transfusion to the patients.