In order to shed light on the discrepant changes in plasma immunoreactive parathyroid hormone (iPTH) during hemodialysis (HD) and ultrafiltration (UF) in end-stage renal failure, the influence of filtration of PTH fragments on the iPTH level in plasma was examined in 2 sets of experiments: in vitro dialysis of <sup>125</sup>I-bPTH 1-84, <sup>125</sup>I-hPTH 1–34 and <sup>125</sup>I-hPTH 53-84 added to plasma was successively performed through a cuprophane membrane. Gel filtration on a Biogel P-100 column and subsequent counting of the eluate were performed with the plasma before and after dialysis, and with the dialysate fluid after dialysis. An ultrafiltrate obtained from a patient with renal failure was also analyzed for iPTH with a ‘C-’ and with an ‘N-terminaΓ antiserum (GP 500 MA and AS 211/32), and so was his plasma before and after UF, and after a subsequent dialysis session. Fluid obtained by lavage of the filter with acetic acid after dialysis was also analyzed. Chromatography with measurements of iPTH in the eluate was performed in each case, and the procedure was repeated applying a different transmembrane pressure. Immunoreactive material found in the concentrated ultrafiltrate, but not in plasma, was characterized by means of dilution curves in different RIA performed with the C-terminal antiserum preincubated with various synthetic PTH fragments. Results showed that intact PTH does not cross the cuprophane membrane during both in vitro dialysis and in vivo UF. The 1-34 fragments are poorly dialyzed in vitro; either they stick to the membrane or they are disintegrated. 53-84 and other low molecular weight (MW) fragments cross the membrane during both in vitro dialysis and in vivo UF and they disappear from the plasma during HD. During UF low MW fragments which were not detected in plasma and which react with both antisera appear in the ultrafiltrate. Characterization of these fragments by RIA reveals that their antigenic site is located within the midregion of the PTH molecule. It is concluded that decline in iPTH levels during in vivo HD reflects not only inhibition of PTH secretion following the increase in plasma calcium, but also passage of carboxyterminal PTH fragments through the filter. In addition, midregion PTH fragments appear in the concentrated ultrafiltrate, which are not detected in the plasma and which also might have been filtered during UF.