Chloroacetaldehyde and thiodiglycolic acid, two metabolites of ifosfamide, interfere with mitochondrial function and may sequester carnitine. Urinary excretion of carnitine was measured in five patients before and during a continuous infusion of ifosfamide over 5 days at a dose of 2.8-3.2 g/m2 per day. The excretion of free and total carnitine increased from 85+/-53 to 2697+/-1393 micromol/day on the 1st day of chemotherapy and then gradually decreased. The average loss of carnitine during a chemotherapy cycle amounted to 8.5 mmol. The formation and excretion of esters of carnitine and metabolites of ifosfamide and/or a decreased renal tubular reabsorption could account for this marked loss, which might lead to symptomatic carnitine deficiency after several chemotherapy cycles.