BACKGROUND: Although the dose of 400 mg/kg body weight intravenous immunoglobulins (IVIG) every 3-4 weeks is now standard for treating patients with common variable immune deficiency, studies demonstrating its long-term benefits over low 200 mg/kg dose and its effects on infectious subsets (upper vs lower respiratory vs non-respiratory infections) are rare. METHODS: All patients from a single center with the diagnosis of common variable immune deficiency and whose clinical chart was available during three successive therapeutic periods [a pre-IVIG replacement period, a low-dose (200 mg/kg every 3 weeks) and a standard-dose replacement period (400 mg/kg every 3 weeks)] were screened retrospectively. RESULTS: Seven patients followed up for a total of 116 patient-years over the three defined periods of observation were recruited. When compared with low-dose therapy, standard-dose intravenous immunoglobulin therapy raised trough IgG levels from 4.3 to 6.5 g/l and significantly decreased the overall frequency of infections, with marked effects on lower respiratory tract and severe infection number. In contrast, non-respiratory and upper respiratory infections were, in comparison, resistant to therapy. CONCLUSIONS: Overall, these data support the use of standard-dose 400 mg/kg intravenous immunoglobulin therapy, despite the high cost, to raise trough IgG levels to 5-7 g/l, but underlines that some categories of infectious events (non-respiratory, upper respiratory) may need parallel surgical or pharmacological approaches to be optimally prevented or treated.