The treatment of anemia in hemodialysis patients is frequently hindered by the presence of suboptimal iron stores. Intravenous iron dextran is in common use to maintain iron stores in this population, but there are little published data regarding the incidence and type of adverse events. The purpose of this study was to evaluate the safety of this medication. Charts from four hemodialysis centers of all 573 patients treated with intravenous iron dextran (INFeD; Schein Pharmaceutical, Inc, Florham Park, NJ) between July 1, 1993, and June 30, 1995, were studied. Twenty-seven patients (4.7%) had adverse reactions that were related to iron dextran. Four patients (0.7%) had reactions classified as serious (one cardiac arrest; three others required hospitalization). Ten patients (1.7%) had reactions classified as anaphylactoid. No patients died or developed permanent disability as a result of reactions. The most common adverse reactions included itching (1.5% of patients) and dyspnea or wheezing (1.5%); others included chest pain (1.0%), nausea (0.5%), hypotension (0.5%), swelling (0.5%), dyspepsia (0.5%), diarrhea (0.5%), skin flushing (0.3%), headache (0.3%), cardiac arrest (0.2%), and myalgias (0.2%). Five of all the reactions occurred during a test dose; four of these were anaphylactoid. Several factors were studied as possible predictors of adverse reactions. A positive history of drug allergy (odds ratio, 2.4; P = 0.03) and history of multiple drug allergy (odds ratio, 5.5; P = 0.0004) were significant predictors of reactions. In summary, we found serious adverse reactions to be uncommon in hemodialysis patients treated with intravenous iron dextran. Future prospective studies will help confirm this finding.