A 21-month-old infant presented with acute obstructive hydrocephalus due to a large tuberculous abscess in the posterior fossa 3 months after starting treatment for miliary tuberculosis. Insertion of a ventriculo-peritoneal shunt resulted in some clinical improvement but subsequent neurological deterioration occurred due to massive enlargement of the tuberculous abscess despite apparently adequate antituberculosis therapy. Repeated drainage procedures of the abscess eventually resulted in resolution and clinical improvement. As part of the workup for poor weight gain and the unusual clinical course, the patient’s acetylation status for isoniazid was determined and found to be very rapid. Doubling the daily dose of isoniazid was followed by a dramatic weight increase and further clinical improvement. Decreasing the load of tuberculous antigen by draining the abscesses and increasing the pulse exposure of isoniazid is the best possible explanation for the clinical improvement finally seen in this patient.