We report a case of a patient on maintenance peritoneal dialysis therapy treated with a high-dose methotrexate regimen for central nervous system lymphoma. For the initial methotrexate cycles, he had received temporary daily high-flux hemodialysis starting 24 hours after the infusion of methotrexate to avoid toxicity. However, on account of issues with vascular access, he was treated with continuous multiple-exchange peritoneal dialysis for the last 2 cycles of chemotherapy. Time-averaged clearances (dose divided by area under the curve, combination of endogenous and dialysis clearance) during treatment with high-flux hemodialysis and continuous multiple-exchange peritoneal dialysis were 0.77 mL/min/kg (0.013 mL/s/kg) and 0.65 mL/min/kg (0.011 mL/s/kg), respectively. Peritoneal clearance of methotrexate was estimated to be 0.124 +/- 0.037 mL/min/kg (0.00207 +/- 0.00062 mL/s/kg). Despite lower clearance by means of peritoneal dialysis compared with hemodialysis, the patient did not develop clinical evidence of methotrexate toxicity.