Attempts at the identification of specific uremic toxins have, to date, been unrewarding and yet there is vogue for the measurement of, and the control by devices of hypothetical levels of, "middle molecular weight" toxins. In an attempt to elucidate whether small or middle molecular weight retention products are responsible for uremic platelet and peripheral nerve conduction defects, 14 patients with end-stage renal disease established on hemodialysis were studied using a conventional hemodialyzer and an experimental device which combined hemodialysis and hemoperfusion and which has enhanced in vitro vitamin B12 clearances. With the latter device reduced BUN and creatinine clearances were encountered and over a 2-month treatment period patient's serum BUN rose. In spite of this, there was improvement in the velocity of platelet aggregation to 10 microM adenosine diphosphate and to a standard collagen preparation associated with treatment by the experimental device. There was not, however, any demonstrable influence made on nerve conduction studies. The study suggests that different uremic retention products influence platelet and peripheral nerve function and that further efforts into studying the function of living cells or systems, in uremia might have better yield in the future guidance of the adequacy of dialysis than will the biochemical measurements of various waste products.