Intermittent dialysis is still the predominant treatment for acute or chronic renal insufficiency in the USA despite increasing evidence that slower and longer fluid management therapies are more beneficial to the patient. We have investigated the use of slow continuous intracorporeal plasmapheresis (SCIP) as a more efficient and hemodynamically stable alternative means of treating acute fluid overload. In this paper we discuss preliminary observations on the safety of SCIP catheter insertion, fluid removal, extraction and pathology in Yorkshire pigs. SCIP catheters removed plasma for extracorporeal plasma water removal without significant gross or histopathological changes. Blood chemistry and cell counts remained stable during therapy. Toxicological studies indicated no pyrogenicity, hemolysis, cytotoxicity, acute systemic toxicity, delayed-type hypersensitivity, or blood recalcification coagulation inhibition. Intracutaneous extracts caused only mild irritation. SCIP therapy appears to be safe for use in the removal of plasma and plasma water from experimental animals.