The incidence of SIADH (the syndrome of inappropriate antidiuretic hormone secretion) was analyzed retrospectively in 43 children who received marrow-ablative chemotherapy before autografts with peripheral blood stem cells for lymphoid malignancies. SIADH was documented in three children (ages 3, 13, and 13 years) who received chemotherapy, which included high-dose methyl 6-[3-(chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) and cyclophosphamide, under a concomitant overhydration protocol. SIADH was manifested as frequent vomiting in two patients and as generalized seizure in one. Hyponatremia (< 125 mEq/L), hypo-osmolality (< 260 mOsm/kgH2O), and continued urinary excretion of sodium (> 30 mEq/L) were used to diagnose SIADH in these three patients. All signs and symptoms subsided within 24 hours either by fluid restriction alone (n = 1) or by supportive care including anticonvulsant and D-mannitol, or hyperhydration with saline plus 5% glucose and diuretic. None of the patients died. Careful monitoring of the serum sodium level, as well as the osmolality of plasma and urine, should be incorporated into the patient management protocol for this type of high-dose chemotherapy.