A large elevation in serum creatinine (S(Cr)) on an unchanged peritoneal dialysis (PD) schedule is usually caused by a decrease in total creatinine clearance (C(Cr)), but may also reflect an increase in creatinine (Cr) production. A meticulously compliant 43-year-old man with lupus nephritis on automated nocturnal PD plus an additional daytime exchange developed a rise in S(Cr) to 16.73 mg/dL from 8.06 mg/dL after starting fenofibrate, while total C(Cr) decreased only to 61.5 L/1.73 m2 from 77.4 m2 weekly. Creatinine excretion was 16.4 mg/(kg x 24 h) pre-fenofibrate. It increased to a high of 26.2 mg/(kg x 24 h) during the period of fenofibrate intake and returned to 21.9 mg/ (kg x 24 h) 2 months after discontinuation of that drug. The patient's age, weight, height, body mass index, 24-h drain and urine volumes, total Kt/V urea, serum urea nitrogen, urea nitrogen excretion, and (for the pre-fenofibrate period) S(Cr), Cr excretion, estimated Cr production, and measured-to-predicted Cr excretion (using a formula developed in PD patients) were within the 95% confidence intervals (CIs) obtained in a control group of 24 other men on similar PD schedules. The patient's Cr excretion and production were above the 95% CIs of the control group while he was on fenofibrate, and they returned toward or within the 95% CIs after cessation of the drug. The patient's serum creatine phosphokinase was not elevated while he was taking fenofibrate. A thorough investigation of the potential mechanisms of a rise in S(Cr) during the course of PD is warranted to determine if the rise is disproportional to any fall in total C(Cr). In the latter case, Cr excretion and production should be evaluated, and if elevated, conditions potentially causing the rise in Cr production (fenofibrate in this patient) should be sought, and appropriate therapeutic interventions should be implemented.