We reviewed the side-effects of intravenous (i.v.) cyclophosphamide (CPM) pulse therapy in a group of 75 patients suffering from various autoimmune disorders (mostly systemic lupus erythematosus and vasculitis) who received a total of 451 i.v. CPM pulses, given on a monthly basis (mean +/- s.d. CPM dose per pulse: 764 +/- 217 mg; mean +/- s.d. follow-up period: 26.7 +/- 22.1 mon). Infection was the most common side-effect (30 episodes in 21 patients; 28% of the patients) but rarely required in-patient treatment (8 episodes in 7 patients; 9% of the patients). No relationship could be found between the occurrence of infection and the dose of CPM or of glucocorticoids. Other side-effects were rare. Only one patient suffered from neutropenia. Haemorrhagic cystitis was never observed nor did premature ovarian failure in the 25 female patients at risk. Four patients developed neoplasia and three died suddenly a few days after receiving a CPM pulse but the causal relationship between CPM therapy and these poor outcomes is speculative. Taken together, our data confirm in a large group of patients that i.v. CPM pulse therapy is relatively safe. In particular, the rate of severe infection requiring in-patient treatment is rare (1.8% of 451 pulses.).