In immunodeficiency patients the lack of immunoglobulins (Ig) can be total or partial with a specific IgG subclass imbalance masked by normal values for total IgG. In the latter case therapy with intravenous IgG preparations (IVIG) is generally beneficial, provided the IVIG preparations used originate from large pools of normal blood donors and exhibit a normal IgG subclass distribution. We have analyzed the subclass distribution of three IVIG products: Sandoglobulin (SAGL), GamimuneN (GI), Gammagard (GG), 6-10 lots each, in four different laboratories. The competitive enzyme immunoassays and radial immunodiffusion methods used different monoclonal and polyclonal antibodies specific for IgG1, IgG2, IgG3, and IgG4, respectively. Despite minor interlaboratory differences, the results show that the slightly lower IgG1 content of SAGL versus GI and GG was quantitatively compensated by a higher proportion of IgG2, that no differences existed in IgG3 levels, but that one preparation (SAGL) contained 2-3% of IgG4 compared to 0.5-1.5% in GI and below 0.5% in GG. This difference was significant, the two latter preparations being at or below the lower limit of what are considered to be normal values found in human adults. Such differences may have important clinical consequences.