In five patients with cirrhosis given an oral methionine load, blood mercaptan concentrations were not significantly affected by neomycin and metronidazole therapy. Methanethiol and dimethyl sulphide rose after methionine to levels encountered in hepatic encephalopathy but in stable cirrhotics no neurological abnormalities were evident. In one patient with chronic hepatic encephalopathy there was no significant change in methanethiol, dimethyl sulphide or ammonia concentration 4 h after methionine when conscious state had deteriorated by two stages of encephalopathy. Elevations in blood methanethiol and dimethyl sulphide concentration in children with congenital hypermethioninaemia were not associated with any neurological or electroencephalographic features of hepatic coma. These studies do not support an important role for mercaptans in hepatic encephalopathy although a synergistic effect cannot be excluded. Furthermore, mercaptans appear to arise from endogenous metabolism rather than bacterial action in the gut.