CNS manifestations were studied in 97 gene carriers of von Hippel-Lindau syndrome (HLS). Haemangioblastomas of the CNS were found in 43 patients (44%), 23 females and 20 males. The mean age at diagnosis was 39 years (12-73 years). A total of 93 haemangioblastomas were detected of which 74% were intracranial and 26% were located in the spinal cord; 75% were predominantly cystic and 25% presented as solid lesions. Multiple lesions were found in 42% of HLS-associated haemangioblastomas, but in none of 51 patients with CNS haemangioblastoma without HLS. Haemangioblastoma was the cause of death in 82% of patients with HLS. Although microsurgery has considerably improved post-operative results, multifocal tumour development and recurrence remain a serious problem in the clinical management of HLS gene carriers.