BACKGROUND: Creutzfeldt-Jakob disease (CJD) in humans and chronic wasting disease (CWD) in deer and elk occur in the United States. Recent reports of 3 unusually young patients with CJD who regularly consumed deer or elk meat created concern about the possible zoonotic transmission of CWD. OBJECTIVE: To examine the possible transmission of CWD to humans. PATIENTS: Three unusually young patients (aged 28, 28, and 30 years) with CJD in the United States during 1997-2000. METHODS: We reviewed medical records and interviewed family members and state wildlife and agriculture officials. Brain tissue samples were tested using histopathologic, immunohistochemical, immunoblot, or prion protein gene analyses. MAIN OUTCOME MEASURES: Presence or absence of established CJD risk factors, deer and elk hunting in CWD-endemic areas, and comparison of the evidence for the 3 patients with that of a zoonotic link between new variant CJD and bovine spongiform encephalopathy. RESULTS: None of the patients had established CJD risk factors or a history of travel to Europe. Two patients hunted game animals and 1 was a daughter of a hunter. Unlike patients with new variant CJD, the 3 patients did not have a unique neuropathologic manifestation, clinicopathologic homogeneity, uniformity in the codon 129 of the prion protein gene, or prion characteristics different from those of classic variants. CONCLUSIONS: Although the occurrence of 3 unusually young patients with CJD who consumed venison suggested a possible relationship with CWD, our follow-up investigation found no strong evidence for a causal link. Ongoing CJD surveillance remains important for continuing to assess the risk, if any, of CWD transmission to humans.