The relationships between predialysis and postdialysis erythrocyte transketolase activities and symptoms of uremic peripheral neuropathy were studied prospectively for 21 months in 19 chronic hemodialysis patients. In all patients the predialysis activity was observed to be sometimes greater and sometimes less than the postdialysis activity. These observations were interpreted as indicating the coexistence in uremic blood of stimulatory and inhibitory substances which influence the enzyme independently. After enzyme stimulation was assumed to be a constant feature of uremia, the expected stimulated activity in erythrocytes of predialysis blood was found to be variably inhibited up to about 55% in these patients. The occurrence of paresthesiae was closely correlated with prolonged erythrocytes transketolase inhibition which in most cases reached a level of about 40%. Our conclusion is that the magnitude of erythroycte transketolase inhibition above a certain minimum level, together with its duration, is associated with symptoms of sensory peripheral neuropathy in the uremic patient. It is therefore predicted that such measurements may be usefully applied in ascertaining the extent of hemodialysis needed to prevent the development of this pathological state.