In these case reports, we investigated pandemic influenza 2009 vaccination of primary hypogammaglobulinaemic patients. Three combined variable immunodeficiency (CVID) patients and one X‐linked agammaglobulinaemia (XLA) patient were vaccinated with the pandemic vaccine A/California/7/2009 (H1N1)‐like split virus (X179a) adjuvanted with the oil‐in‐water emulsion AS03. Subsequently, serum and peripheral blood mononuclear cells were sampled and used to measure the haemagglutination inhibition (HI) and antibody‐secreting cell (ASC) responses. In addition, the IFN‐γ, IL‐2 and TNF‐α producing CD4⁺ Th1‐cell response was determined as these cytokines are important indicators of cell‐mediated immunity. Two of the CVID patients responded to vaccination as determined by a >4‐fold rise in HI antibodies. These subjects also had influenza‐specific ASC numbers, which, albeit low, were higher than prevaccination levels. In addition, vaccination induced CD4⁺ Th1‐cell responses in both the XLA patient and the CVID patients, although the frequency of influenza‐responsive cells varied amongst the patients. These results suggest that hypogammaglobulinaemia patients can mount a CD4⁺ Th1 cell‐mediated response to influenza vaccination and, additionally, that influenza vaccination of some hypogammaglobulinaemia patients can produce an influenza‐specific humoral immune response. The findings should be confirmed in larger clinical studies.