Arizona is home to four species of skunks, and rabies is enzootic in the region in which their ranges overlap. Examination of state health data from 1985 to 2004 revealed an irregular 4–10 yr periodicity in the number of cases annually, which may be related to past precipitation patterns. The number of rabid skunks peaked during springtime. Locations of rabies epizootics changed over time, but there was no evidence of a large-scale geographic spread. Skunks live-trapped during 1996–2002 had a low prevalence of rabies-virus neutralizing antibodies. This study was the first to document rabies in hooded skunks (Mephitis macroura).