During the last decade, the availability of monoclonal antibodies against human IgG subclasses led to a marked increase in serum Ige subclass determinations, including in routine laboratories. Although several drawbacks of polyclonal antisera (poor specificity except in certain precipitation assays, inter-batch variability, etc) are avoided by the use of monoclonal antibodies, a number of methodological difficulties and pitfalls still remain, especially for measurement of IgG2 and with commercial kits. Moreover, most of them are hardly practicable, because of arbitrary standardization and absence of appropriate normal reference values. This increase in routine serum Ige subclass level determination led to a considerable widening of patient recruitment and a significant evolution of patterns and frequencies of subclass deficiencies was observed in patients with unexplained infection and no characterized immunodeficiency syndrome, as compared with initial studies performed in specialized clinical immunology departments. IgG3 deficiency is more frequent in mildly than in severely infected patients, and a marked decrease in the incidence of IgG2 deficiency was found in our recent survey. We also present the results of a recent retrospective study on hypogammaglobulinemia. In this condition, IgG subclass imbalances are more frequent than an overall IgG subclass decrease, and IgG2 deficiency appears to be a marker of severity. Other observations are: 1) the high frequency of selective IgG1 deficiency, especially in adults over 40 years; and 2) that of TgG2 deficiency in children of less than 4 years of age.