A 12-year-old girl with protracted tuberculous meningitis received standard chemotherapy and dexamethasone and had a progressive cerebrospinal fluid neutrophilia, raised protein and depressed glucose levels. Her temperature was raised for 5 months until a second course of dexamethasone was given. At week 15, multiple tuberculomas and hydrocephalus were detected followed by acute hydrocephalus (week 58), which required a ventricular-peritoneal shunt. Tuberculomas resolved after a second course of dexamethasone but recurred 15 months later. Immunological investigations were normal including integrity of the type 1 cytokine pathway. From month 24, interferon-γ was given subcutaneously (initially 50 μg/m²) and continued for 19 months. Within 2 weeks she responded clinically followed by a reduction in inflammatory signs on magnetic resonance imaging scan (but not in the tuberculomas). At month 44, when chemotherapy was stopped, the cerebrospinal fluid/serum albumin quotient was 57×10⁻³ (normal <6·0×10⁻³), which supports continuing major impairment of the blood–brain barrier. Gene expression in peripheral blood mononuclear cells before and during treatment with interferon-γ, assessed by gene array analysis, showed reduction in a number of cytokine and chemokine genes. The response to interferon-γ might have been secondary to downregulation of certain cytokine and chemokine genes.