Inability to accurately diagnose infection in granulocytopenic patients is a major cause for morbidity and mortality, and prompted this study of 344 infections (pharyngitis, skin infection, pneumonia, anorectal infection, and urinary tract infection) in a select group of cancer patients. Strikingly similar alterations in clinical presentation were found for all infections that developed in profoundly granulocytopenic patients. Physical findings of exudate, fluctuation, ulceration or fissure, local heat, swelling, and regional adenopathy were all less prevalent in the granulocytopenic patient, while fever was much more common. Only erythema and local pain or tenderness were present in practically all patients regardless of site of infection or level of granulocyte count. A better understanding of how granulocytopenia affects the presentation of infection should lead to earlier and more accurate diagnosis and potentially to more successful therapy.