Abstract Polyacrylamide-gel electrophoresis was used for differential diagnosis of radicular cysts and granulomas. Root canal fluids were aspirated from forty anterior teeth with radiographic evidence of periapical pathosis, and from one pulpless anterior tooth with no radiographic evidence of periapical pathosis. Endodontic therapy was performed on all the teeth, and all the periapical lesions were surgically removed. The lesions were examined histologically, and the histopathologic diagnoses were then compared with the electrophoretic patterns. Analysis of the root canal fluids showed the following: (1) An albumin pattern was found in all thirty-one of the cases diagnosed histologically as being granulomas. The same pattern was also found in the case of the pulpless tooth without an area of rarefaction. (2) In eight of the nine cases diagnosed histologically as cysts, there was a much more intense albumin pattern and other patterns in the globulin regions. In the one case of a cyst that was misdiagnosed, the apical portion of the canal was calcified and the cyst lumen was never penetrated.