Pseudomonas pseudomallei, which causes melioidosis, is most commonly associated with pulmonary infection. We describe seven patients who developed a neurological syndrome as the predominant manifestation of melioidosis: this syndrome was characterized by peripheral motor weakness (mimicking Guillain-Barré syndrome), brain-stem encephalitis, aseptic meningitis, and respiratory failure. Neurological melioidosis occurred in the absence of demonstrable foci of infection in the central nervous system (CNS) in five of six patients whose cerebrospinal fluid was available for culture. Computed tomography and magnetic resonance imaging of the brain and spinal cord of these patients were not suggestive of pyogenic infection, although the latter procedure detected brain-stem encephalitis. Autopsy findings in one case confirmed brain-stem encephalitis without evidence of direct bacterial infection. The clinical presentation of neurological melioidosis includes features of an exotoxin-induced neurological syndrome, with profound neurological disease occurring in the absence of apparent direct infection of the CNS. This syndrome appears to be a newly recognized clinical presentation of melioidosis.