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Substantial derangements of mesothelial biology are observed during experimental simulations of dialysis conditions, inferred from the content of human dialysis effluent and visualized by microscopy of human mesothelial biopsies. Canosmotically active solutions be made biocompatible with the osmoregulatory system of the mesothelium? Can the contributions of the mesothelium to host defenses against inflammation and/or infection be supported during CAPD? Do underlying metabolic derangements present in various kidney diseases and end-stage renal disease, regardless of cause, require customized CAPD protocols and solutions? Use of dialysis solutions less directly toxic to the mesothelium is a necessary step toward some day manipulating peritoneal biology by pharmacological and therapeutic modalities.