In May 1993, an outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States was caused by the previously unrecognized Sin Nombre virus (SNV). Most HPS patients had an influenza-like prodrome, followed by rapid onset of pulmonary edema (fatality rate, 52%). To define the magnitude of the outbreak, patients with milder illnesses who sought medical care in the outbreak area during the outbreak period were assessed for infection with SNV. Of 299 study subjects, 43 had illnesses similar to the HPS prodrome. One laboratory finding, thrombocytopenia, was highly discriminatory between non-HPS patients (1%) and confirmed HPS patients (71%; P < .001) during the prodrome phase. No study subject had serologic evidence (IgM antibodies) of recent SNV infection. Five had IgG titers consistent with a previous hantavirus infection: 3 of these 5 were among the 43 patients who had illnesses similar to the HPS prodrome (P < .05). These data provide evidence that mild illness is rarely caused by SNV.