To identify the factors associated with a poor outcome, we reviewed the records of 28 patients with tularemia diagnosed between 1974 and 1984. Most of the patients were men between the ages of 35 and 45 years, who presented with ulceroglandular tularemia. Twelve patients had the anticipated rapid response to therapy, with resolution of their presenting symptoms within one week (group A). Surprisingly, the majority (16 [58%] of 28) had a more prolonged or fatal illness (group B). Group B patients more often had a serious underlying medical disorder, and waited longer before seeking medical attention. Only patients in group B presented with electrolyte or renal function abnormalities (31%), pneumonia and pleural effusions (25%), elevated serum creatine phosphokinase levels (25%), and Francisella tularensis bacteremia (12.5%). Sterile pyuria, however, was an unexpectedly frequent finding in both groups. Group B patients more often experienced a prolonged delay from the time of physician contact to therapy, and were not treated with an aminoglycoside; relapse (12.5%) and death (6.2%) occurred only in group B. Thus, earlier and more appropriate intervention by the physician may have prevented some of the increased morbidity in our patients. These findings suggest that rapid presumptive aminoglycoside therapy (gentamicin sulfate or streptomycin sulfate) should be considered soon after tularemia is suspected, especially for patients with serious underlying medical disorders.