The clinical features of 130 cases of aseptic meningitis syndrome associated with ECHO virus type 6 infection were studied. Characteristically, the onset was acute with the development of fever, headache, muscle pains, and vomiting. A biphasic course was present in 8% of the cases. The physical findings included mild to moderate stiffness or spasm of the neck, back, and posterior thigh muscles. Disturbance in sensorium, cranial nerve involvement, and bulbar signs were conspicuously absent. Absence of deep tendon and superficial reflexes occurred in 16% of the cases. Evidence of mild muscle weakness occurred in 39% of cases, more commonly in the axial rather than peripheral muscles. Most of these patients had bilateral weakness of the anterior neck muscles, but included in the group were five with bilateral weakness of the back or abdominal muscles and six with some involvement of the extremities. Neuromuscular changes were mild and frequently questionable. Where follow-up was available, the changes were usually found to be transient. The effect of age upon the clinical picture was analyzed. Only 3 of 130 patients were less than 4 years of age. Young children had a more acute onset and were admitted to the hospital more promptly than older children and adults. The incidence of pleurodynia was 38% in adults and only 5% in patients less than 20 years of age. The cerebrospinal fluid revealed pleocytosis, with lymphocyte counts ranging from a few cells to 930/mm3. The protein values exceeded 40 mg/100 ml in 48% of the cases, the highest value being 102 mg/100 ml. An undifferentiated febrile illness in household associates of patients with aseptic meningitis, characterized by headache, vomiting and muscle pain, was associated with a high recovery rate of ECHO 6 virus. This is presumably the forme fruste of the fully developed aseptic meningitis syndrome. ECHO 6 virus was recovered from four patients in whom there was evidence of neurologic involvement beyond that seen in the aseptic meningitis syndrome. ECHO 6 virus was the probable etiologic agent in two of these cases. A 15-year-old girl with mild encephalitis marked by disorientation, hallucinations, and weakness of the legs yielded ECHO 6 from her alimentary tract. ECHO 6 was recovered from the cerebrospinal fluid and alimentary tract of a 15-year-old boy with features of the Guillain-Barré syndrome.