Rickettsialpox, a spotted fever rickettsiosis, was first identified in New York City (NYC) in 1946. During the next five years, approximately 540 additional cases were identified in NYC. However, during the subsequent five decades, rickettsialpox received relatively little attention from clinicians and public health professionals, and reporting of the disease diminished markedly. During February 2001 through August 2002, 34 cases of rickettsialpox in NYC were confirmed at CDC from cutaneous biopsy specimens tested by using immunohistochemical (IHC) staining, PCR analysis, and isolation of Rickettsia akari in cell culture, as well as an indirect immunofluorescence assay of serum specimens. Samples were collected from patients with febrile illnesses accompanied by an eschar, a papulovesicular rash, or both. Patients originated predominantly from two boroughs (Manhattan and the Bronx). Only 8 (24%) of the cases were identified prior to the reports of bioterrorism-associated anthrax in the United States during October 2001, and lesions of several patients evaluated during and subsequent to this episode were suspected initially to be cutaneous anthrax. IHC staining of biopsy specimens of eschars and papular lesions were positive for spotted fever group rickettsiae for 32 patients. Of the eleven patients for whom paired serum samples were obtained, all demonstrated fourfold or greater increases in antibody titers reactive with R. akari. The 17-kDa protein gene sequence of R. akari was amplified from eschars of five patients. Four isolates of R. akari were obtained from cutaneous lesions. Possible factors responsible for the increase in clinical samples evaluated for rickettsialpox during this interval include renewed clinical interest in the disease, improved diagnostic methods, epizootiological influences, and factors associated with the recent specter of bioterrorism.