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Objective: To determine the cause of acute illness on August 30, 2000, among patients at an outpatient dialysis center (center A)., Design: We performed a cohort study of all patients receiving dialysis on August 30, 2000; reviewed dialysis procedures; and analyzed dialysis water samples using microbiologic and chemical assays., Setting: Dialysis center (center A)., Patients: A case-patient was defined as a patient who developed chills within 5 hours after starting hemodialysis at center A on August 30, 2000., Results: Sixteen (36%) of 44 patients at center A met the case definition. All case-patients were hospitalized; 2 died. Besides chills, 15 (94%) of the case-patients experienced nausea; 12 (75%), vomiting; and 4 (25%), fever. Illness was more frequent on the second than the first dialysis shift (16 of 20 vs 0 of 24, P < .001); no other risk factors were identified. The center's water treatment system had received inadequate maintenance and disinfection and a sulfurous odor was noted during sampling of the water from the reverse osmosis (RO) unit. The water had elevated bacterial counts. Volatile sulfur-containing compounds (ie, methanethiol, carbon disulfide, dimethyldisulfide, and sulfur dioxide) were detected by gas chromatography and mass spectrometry in 8 of 12 water samples from the RO unit and in 0 of 28 samples from other areas (P < .001). Results of tests for heavy metals and chloramines were within normal limits., Conclusions: Parenteral exposure to volatile sulfur-containing compounds, produced under anaerobic conditions in the RO unit, could have caused the outbreak. This investigation demonstrates the importance of appropriate disinfection and maintenance of water treatment systems in hemodialysis centers.