We prospectively examined the epidemiology of invasive Haemophilus influenzae type b (Hib) infections among children under 5 y of age in the Greater Athens area before the introduction of immunization. The annual incidence of systemic Hib infections was 12/100000. Meningitis was the most common clinical entity and accounted for 69% of the cases. In the prevaccine era, the incidence of systemic Hib disease, particularly that of meningitis, was much lower in Greece compared to rates reported from Northern and Central Europe.