BACKGROUND Cyclophosphamide is an alkylating agent and was traditionally known to potentiate the renal action of vasopressin. Although low-dose intravenous pulse cyclophosphamide therapy is being used extensively in the treatment of malignant and rheumatological diseases, there have been only a few case reports of cyclophosphamide-induced hyponatraemia. METHODS Clinical data were retrospectively analysed from 84 patients (42 lupus nephritis; 42 non-Hodgkin's lymphoma; a total of 112 treatment episodes) admitted for intravenous pulse cyclophosphamide (500-750 mg/m(2)) therapy. In all patients, half-isotonic saline was used for prophylactic hydration. Cyclophosphamide-induced hyponatraemia was defined as serum sodium concentration <135 mEq/L at 24 hours after the therapy in patients whose basal serum sodium concentrations were normal. RESULTS After the low-dose intravenous pulse cyclophosphamide, serum sodium concentration significantly decreased from 139.9 +/- 3.5 to 137.9 +/- 5.1 mEq/L (P < 0.001). Cyclophosphamide-induced hyponatraemia occurred in 15 treatment episodes (13.4%) from 12 patients (14.3%). Patients with hyponatraemia were significantly older than those without hyponatraemia (57.3 +/- 14.7 vs. 40.0 +/- 17.0 years, P < 0.01). Hyponatraemia was associated with male sex on univariate analysis (P < 0.05), but not on multivariate analysis. No factors were found to independently predict the occurrence of cyclophosphamide-induced hyponatraemia when multivariate analysis was performed including parameters age, sex, underlying disease, presence or absence of comorbidities associated with hyponatraemia, presence or absence of concurrent medications associated with hyponatraemia and dose of cyclophosphamide. CONCLUSIONS Hyponatraemia occurring after low-dose intravenous pulse cyclophosphamide is not rare, especially when hypotonic solutions are adopted for hydration protocol. Thus, the use of hypotonic fluids should be avoided when using cyclophosphamide. Instead, isotonic solutions should be used if a forced diuresis is required.