M-proteins are monoclonal immunoglobulins or immunoglobulin fragments that aberrantly accumulate in the plasma. Hemodialysis (HD) patients with M-proteins may, under certain circumstances, also need therapeutic plasma exchange (TPE). We employed a protocol for tandem TPE/HD in patients with M-protein disorders. We followed the urea reduction ratio (URR), a measure of the efficiency of HD, to compare the effect of TPE on HD efficiency during tandem procedures versus the efficiency of HD performed as a stand-alone procedure in the same patients. Three men (J.M., R.T., M.M.) underwent 23, 80, and 25 tandem TPE/HD over 3, 17, and 7 months, respectively, almost all in the outpatient setting. Mean whole blood flow rate (in ml/min) was slower during hemodialysis alone than during TPE/HD for J.M. (289 ± 24 vs. 332 ± 22, P < 0.0001) and R.T. (310 ± 20 vs. 367 ± 15, P < 0.0001) but not for M.M. (395 ± 65 vs. 404 ± 62, P = 0.6844). URR was equivalent during hemodialysis alone and during TPE/HD for J.M. (54 ± 4.2 vs. 58 ± 1.4, P = 0.3333), R.T. (69 ± 4.9 vs. 70 ± 2.5, P = 0.9804), and M.M. (71 ± 2.4 vs. 67 ± 1.5, P = 0.1143). J.M.'s renal function recovered sufficiently to permit discontinuation of hemodialysis. R.T. experienced both subjective and objective improvement of his arthritic symptoms. M.M. achieved hemostatic control but ultimately died of amyloidosis. TPE/HD is feasible using disparate pieces of equipment when the therapeutic plasma exchange circuit is connected in parallel with the low-pressure side of the hemodialysis circuit. Our experience illustrates that therapeutic plasma exchange did not adversely impact hemodialysis when the two procedures were performed in tandem. J. Clin. Apheresis 2005.© 2005 Wiley-Liss, Inc.