Erythrocyte transketolase activity (ETKA) was determined in ten uremics undergoing long-term hemodialysis and in four patients treated with Giordano-Giovanetti diet therapy. Transketolase is an essential enzyme in the pentose phosphate shunt and plays a role in myelin sheath maintenance. Its co-factor is thiamine pyrophosphate. In thiamine deficient states ETKA is depressed. ETKA predialysis was depressed in six chronic uremics, although all received thiamine. Dialysis restored ETKA toward normal. Diet patients had depressed transketolase activity which was not affected by diet therapy despite reduced blood urea nitrogen levels. Uremic plasma inhibited normal ETKA by an average of 31.2%; inhibition was reversed by dialysis. A low weight molecular fraction (<500) obtained from dialysates of uremic subjects inhibited normal ETKA. Low weight dialyzable toxin(s) accumulates in the plasma of uremics, which inhibits ETKA and may play a role in the development of uremic polyneuropathy.