A 14 day old baby presented with signs of an acute encephalitis. Clinically, herpes simplex encephalitis (HSE) was suspected. Early MRI and EEG were normal and there was rapid clinical improvement. A negative polymerase chain reaction (PCR) result on the initial CSF sample seemed to make HSE most unlikely. This diagnosis was subsequently proved after demonstration of specific antibody production using immunoelectrophoresis of the CSF. The child had extensive damage to brain tissue. The need for sequential analysis of CSF in making or refuting this diagnosis is illustrated.