This study analyzes the clinical and bacteriologic features of CSF infections that occurred in patients with neoplastic meningitis treated with thiotepa and methotrexate administered through a subcutaneous reservoir and ventricular catheter (SRVC). Thirty-one patients were treated, and CSF infections occurred in four (13%). Staphylococcus epidermidis was the infecting organism in each case and Pseudomonas maltophilia occurred with S epidermidis in one patient. Fever, headache, lethargy, and evidence of CSF extravasation around the SRVC were the common manifestations of infection. The CSF leukocytosis was the only laboratory abnormality noted. All infections were cured with the appropriate antibiotics and removal of the SRVC. Risk of CSF infection did not seem to be related to the use of high doses of dexamethasone, cranial radiation therapy, or the presence or absence of leukopenia. The SRVCs were replaced and treatment of neoplastic meningitis was resumed in three patients; infection did not recur. A CSF infection during management of neoplastic meningitis may be treated effectively and does not preclude adequate therapy of neoplastic meningitis.