Herpes simplex virus (HSV) has veen associated with a variety of inflammatory neurologic disorders. Recently we studied a patient with Guillain-Barré syndrome (GBS) following acute herpes vaginalis infection. Since IgM virus-specific antibody is thought to be a reliable indicator of acute viral infection, we employed a 2-h serologic assay for serum IgM antibodies to HSV using an indirect immunofluorescent technique. This patient demonstrated high serum IgM titers to HSV type 2 during the acute phase of her neurologic syndrome. The titer dropped substantially as convalescence progressed. A search for similar elevations in HSV-IgM specific antibody was made on sera from more than 70 other GBS patients. No other significant IgM antibody titers to either HSV type 1 or type 2 were found in this GBS series and a large number of neurologic controls. However, sera from two patients with a presumptive diagnosis of acute herpes encephalitis based on clinical and cerebrospinal fluid findings were positive, showing high titers in our test. The results of this study suggest that associated acute HSV infection is uncommon in GBS and an immunofluorescent seroassay of the type reported here may be a valuable noninvasive technique enabling the clinical laboratory to rapid confirm a diagnosis of herpes encephalitis.