The IgG4 is the predominant antibody response in patients receiving chronic exposure to high doses of antigen, and this seems to be true for immunotherapy as well. The duration and the dose of immunotherapy (IT) seems to increase specific IgG4 levels, but this increase does not seem to be related to the clinical response, seasonal exposure, duration of disease, and IgE antibody levels. The measurement of IgE and IgG4 antibodies to allergens did not predict the clinical effect of immunotherapy in our study. However, it indicated that the patients were continuing to receive the allergenic extracts and that the extract used in vivo, although produced by a different manufacturer, was closely resembling the one used for coating plastic wells in the FAST assay. The increase of antibody titres demonstrate that long term monitoring of IT administration may be accomplished by these in vitro tests, although individual patients may exhibit different responses in time but similar clinical results. Longitudinal studies on a cohort of atopic subjects may help define more precisely doses and timings required to achieve useful indications on both compliance with IT injections and predictivity of its outcome.