The aim of the study was to assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. It was carried out as a 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark, and included 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. The main outcome measure was death. We found that 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio for death in patients treated with antibiotics was high (3.2; 95% CI 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. It is concluded that pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings and provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.