Simple SummaryWe analyzed signs occurring among domestic and wild terrestrial animal species with raccoon rabies variant virus in Massachusetts, 1992–2010. While aggression is a useful predictor of rabies among wild animals, combinations of other signs such as ataxia, disorientation, and salivation are useful predictors of rabies among domestic animals.AbstractWe analyzed signs occurring among domestic and wild terrestrial animal species infected with raccoon rabies variant virus (RRV) in Massachusetts, 1992–2010. The clinical sign of aggression was significantly associated with rabid stray cats (odds ratio, OR = 2.3) and RRV affected major wild terrestrial animal species individually, which included raccoons (OR = 2.8), skunks (OR = 8.0), gray foxes (OR = 21.3), red foxes (OR = 10.4), woodchucks (OR = 4.7) and coyotes (OR = 27.6). While aggression is a useful predictor of rabies among wild animals, combinations of other signs such as ataxia, disorientation, and salivation are useful predictors of rabies among domestic animals. Pets reported with multiple clinical signs had significantly higher rabies positive testing result than those reported with single clinical sign (p < 0.001). The result suggested the importance of avoiding aggressive terrestrial wild animals and giving additional attention to pets with multiple clinical signs.