Therapeutic plasma exchange (TPE) has been used extensively for over 2 decades to treat a variety of autoimmune and congenital diseases and is now widely accepted. The primary objective of this study was to compare the clinical efficacy of two plasma exchange preparations, human serum protein (HSP) and human albumin (HA). Twenty-four patients in the following disease categories underwent TPE using either HSP (Biseko, 5%) or HA (5%): systemic lupus erythematosus, 8; glomerulonephritis, 8; myasthenia gravis, 2; Guillain-Barré-syndrome, 2; recurrent iritis, 1; pemphigoid, 1; uveitis, 1; and vascular retinitis, 1. There was no statistically significant difference in the average number of TPEs needed in the HSP group (13.5) and HA (13.8) measured over the first 6 weeks of treatment. The secondary parameters, in particular the immunological parameters IgG and IgA, provided evidence that plasma exchange with HSP may have some advantages over HA, and confirmatory studies in a larger group of patients are indicated. Adverse events during TPE occurred in both the HAS group (4 patients) and the HA group (4 patients). However, patients in the HSP group were older (12.3 years), were suffering from more complicated autoimmune diseases, and the number of occasions (days) on which these were reported (6 days) was less than in the HA group (11 days). One patient in the HA group died from septic-toxic circulatory collapse on Day 49 due to an infection with resistant strains of Staphylococcus aureus. Infections in other patients did not occur; all showed considerable improvement in their symptoms and completed the study in good general condition.