Beta-gamma bridging (β-γ bridging) on serum protein electrophoresis is touted as being virtually pathognomonic for hepatic disease. However, the criteria for β-γ bridging are not defined, and few publications support a relationship between β-γ bridging and liver disease. The goal of this retrospective study was to evaluate the prevalence of hepatic pathology in animals with β-γ bridging. All serum protein electrophoretograms from clinical patients generated at the University of Georgia between 1994 and 2008 were evaluated for the presence of β-γ bridging, defined as (1) an albumin:globulin ratio below the reference interval; (2) indistinct separation between all β and γ globulin fractions or between the β(2) and γ fractions, with a negative shoulder slope of < 5%; and (3) predominance of γ proteins versus β proteins. Of the 237 electrophoretograms examined, 25 (11 dogs, 11 cats, 3 horses) met the inclusion criteria for β-γ bridging. Patients were classified into disease categories on the basis of biochemical, cytologic, and/or histologic findings. Positive predictive values of β-γ bridging for hepatic and infectious diseases were determined with a one-sided exact binomial test. Of 25 animals, 8 had evidence for hepatic disease, whereas 9 had infectious diseases. As such, the positive predictive value of β-γ bridging for hepatic disease was 32.0%, with a 95% confidence interval of 15.0% to 53.5% (P < .001), whereas for infectious disease, the positive predictive value was 36.0%, with a similar confidence interval. Beta-gamma bridging is not pathognomonic for liver diseases and is as frequently found with infectious diseases.