Matrix metalloproteinases (MMPs) are associated with chronic neurologic diseases such as multiple sclerosis and senile dementia. Lyme disease is a multisystemic infection involving the nervous system, skin, joints, and heart. Neurologic manifestations of chronic Lyme disease include encephalopathy and cranial and peripheral neuropathy. Borrelia burgdorferi, the spirochaete causing Lyme disease, has been cultured from the cerebrospinal fluid (CSF), and B. burgdorferi DNA is frequently detected in the CSF of patients with Lyme neuroborreliosis. We used cerebral and cerebellar primary cultures to determine whether B. burgdorferi induces the production of MMPs by primary neural cultures. B. burgdorferi in a dose- and time-dependent manner induced the expression of MMP-9 by primary neural cultures but had no effect on the expression of MMP-2. Human and rat type I astrocytes expressed MMP-9 when incubated with B. burgdorferi in the same manner as primary neural cultures. This response may play a role in the symptomatology and the pathogenesis of Lyme neuroborreliosis.