Antigen-specific plasmablasts appear transiently in peripheral blood after vaccination with influenza or other vaccines (Brokstad et al., 1995; Bernasconi et al., 2002; Sasaki et al., 2007; Wrammert et al., 2008) , but the kinetics of their appearance and persistence during an ongoing infection remain unclear. Here, we have analyzed the magnitude and specificity of the plasmablast response in blood samples taken within weeks after onset of clinical symptoms of pandemic H1N1 influenza virus infection. Using a virus-specific ELISPOT assay, it was possible to show a significant number of pandemic H1N1-reactive plasmablasts in the blood of the infected patients, whereas none were detectable in a cohort of healthy volunteers (Fig. 1, A and B ). These cells were also readily detectable several weeks after symptom onset in the more severe cases. Fig. 1 (A and C) illustrates that, of the total IgG-secreting cells, over half of the cells were producing antibodies that bound pandemic H1N1 influenza virus. Moreover, plasmablasts specific for HA occurred at 30-50% the frequency of virus-specific cells (Fig. 1, C and D) , the specificity most likely to be critical for protection. Most patients also had a relatively high frequency of plasmablasts, forming antibodies that bound to past, seasonal influenza strains ( Fig. 1 C) or recombinant HA from the previous annual H1N1 strain, A/Brisbane/59/2007. Based on the overall frequency of pandemic H1N1-specific cells, it is likely that the cells binding other strains were overlapping populations and cross-reactive. None of the induced plasmablast cells bound to recombinant HA from the H3N2 strain from the same vaccine (A/Brisbane/10/2007). These findings demonstrate that influenza-specific human plasmablasts are continuously generated throughout an ongoing infection and that a fairly high proportion of these cells make antibodies that also cross-react with previous annual H1N1 influenza strains.