Hantavirus pulmonary syndrome (HPS) is a rodentborne viral disease characterized by severe pulmonary illness and a case-fatality ratio of 30%-40%. Sin Nombre virus causes the majority of HPS cases in the United States, and the deer mouse (Peromyscus maniculatus) is its predominant reservoir. This report describes an increase in human cases of HPS reported during January-March 2006 from Arizona, New Mexico, North Dakota, Texas, and Washington state. The findings emphasize the need for renewed attention to reducing the risk for hantavirus exposure.