Primary amebic meningoencephalitis (PAM) is a rare but nearly always fatal disease caused by infection with Naegleria fowleri, a thermophilic, free-living ameba found in freshwater environments. Infection results from water containing N. fowleri entering the nose, followed by migration of the amebae to the brain via the olfactory nerve. In 2007, six cases of PAM in the United States were reported to CDC; all six patients died. This report summarizes the investigations of the cases, which occurred in three southern tier states (Arizona, Florida, and Texas) during June-September and presents preliminary results from a review of PAM cases during 1937-2007. Because deaths from PAM often prompt heightened concern about the disease among the public, an updated and consistent approach to N. fowleri risk reduction messages, diagnosis and treatment, case reporting, and environmental sampling is needed.