The aims were to (1) investigate the aetiology of probable meningococcal disease, where a clinical diagnosis is made in the absence of laboratory data, and (2) evaluate the impact of the Men C vaccination programme in England and Wales. Multiple linear regression analyses were carried out using data reported to Enhanced Surveillance of Meningococcal Disease (ESMD) and laboratory reports of isolates of organisms causing symptoms that mimic meningococcal disease. Confirmed meningococcal disease appeared to be a significant predictor of probable disease. Thus, an additional reduction in meningococcal disease attributable to the serogroup C vaccination campaign was evident in probable disease over and above that observed in confirmed cases alone. Enteroviruses were a significant contributor to cases of probable meningitis and influenza appeared to be a significant contributor to probable cases of septicaemia. This analysis confirms the success seen following the Men C vaccination campaign and gives an indication of the aetiologies of other causes of probable meningitis and septicaemia reported to ESMD.