In October 2001, four cases of inhalational anthrax occurred in workers in a Washington, D.C., mail facility that processed envelopes containing Bacillus anthracis spores. We reviewed the envelopes' paths and obtained exposure histories and nasal swab cultures from postal workers. Environmental sampling was performed. A sample of employees was assessed for antibody concentrations to B. anthracis protective antigen. Case-patients worked on nonoverlapping shifts throughout the facility, suggesting multiple aerosolization events. Environmental sampling showed diffuse contamination of the facility. Potential workplace exposures were similar for the case-patients and the sample of workers. All nasal swab cultures and serum antibody tests were negative. Available tools could not identify subgroups of employees at higher risk for exposure or disease. Prophylaxis was necessary for all employees. To protect postal workers against bioterrorism, measures to reduce the risk of occupational exposure are necessary.