Plasma exchange (PE) is a treatment modality frequently used for many autoimmune diseases and may cause extracorporeal elimination of antibiotics. No data currently exist on antibiotic concentrations in extracellular fluid during PE. The aim of this study is to describe the effect of PE on the serum and subcutaneous tissue pharmacokinetics of piperacillin administered as a continuous infusion in a critically ill 17-year-old patient with Guillain-Barré syndrome and ventilator-associated pneumonia on Days 1 and 4 of antibiotic therapy. The effect of PE on piperacillin concentrations appears to be small. On Day 1, an estimated 7% of total piperacillin eliminated during PE was attributable to PE. On Day 4 this was estimated to be 11%. Using the in vivo sampling technique microdialysis, we have been able to show that a small redistribution of piperacillin from tissue to serum occurs in response to the reducing serum concentrations caused by PE. In critically ill patients, we believe that administration of a beta-lactam antibiotic by continuous infusion should be considered to maintain serum and tissue concentrations of these time-dependent antibiotics.