Seven hundred and nine patients fell ill in southern Germany (Baden-Württemberg) after infection with the tick-borne encephalitis (TBE) virus between 1994 and 1998. Detailed clinical and epidemiological data on TBE were available for 656 patients. A biphasic course of the disease occurred in 485 patients (74%). TBE presented as meningitis in 320 patients (49%), as meningoencephalitis in 270 (41%) and as meningoencephalomyelitis in 66 (10%). Eight of the patients (1.2%) died from TBE. Four hundred and forty-five patients (68%) had noticed a tick bite and the first symptoms occurred, on average, 7 days later. The most frequent neurological symptoms were impairment of consciousness (31%), ataxia (18%) and paresis of the extremities (15%) and cranial nerves (11%). Laboratory investigations revealed leucocytosis in the peripheral blood in 224 out of 392 patients (74%), elevation of the erythrocyte sedimentation rate in 223 out of 245 (91%), increased C-reactive protein in 127 out of 155 (82%), pleocytosis in the CSF of all patients tested, damage of the blood-CSF barrier in 255 out of 322 (79%), abnormalities in EEG in 165 out of 214 (77%) and abnormalities in MRI in 18 out of 102 (18%). In general, adolescents up to 14 years of age had a more favourable course of the disease than adults. Of 230 patients who were re-examined at a later time, 53 (23%) had moderate or severe sequelae. Patients with sequelae presented more frequently (P < 0.001) with impaired consciousness (Glasgow Coma Scale < 7), ataxia, pareses of the extremities or cranial nerves, a need for assisted ventilation, abnormal findings in MRI, pleocytosis > 300 cells/microl and impairment of the blood-CSF barrier (total protein > 600 mg/l). In view of the severity of the illness and the high frequency of sequelae, active immunization against TBE is recommended for all subjects living in and travelling to areas of risk. Prevention of TBE by post-exposure prophylaxis with hyperimmunoglobulins is less effective and therefore should be performed only when absolutely necessary.