Mitomycin-induced hemolytic uremic syndrome (HUS) is a life-threatening complication of this therapy, and increased levels of circulating immune complexes and hypocomplementemia have been found in some patients. We further characterize the role of immune complexes in mitomycin-HUS by showing that removal of these complexes by immunoadsorption with staphylococcal protein A columns correlates with temporal improvement in the microangiopathic hemolytic anemia in this disorder. Two immune complexes bound to the protein A column were identified: an 11S platelet-aggregating protein and a 15S non-platelet-aggregating protein. In addition, the patient had anaphylactoid reactions at the onset of immunoadsorption similar to first-use dialysis reactions that correlated with increases in complement 3a and 5a, interleukin-1 (IL-1), IL-6, and tumor necrosis factor levels. This case suggests that platelet-aggregating and complement-fixing circulating immune complexes are, in part, a proximate cause for mitomycin C-induced HUS. Therapy for mitomycin (HUS) with protein A columns should continue until circulating immune complexes reach undetectable levels and serum complement levels return to the normal range.