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The occurrence of antibodies belonging to IgG class of immunoglobulins with specificity for short ragweed and Bermuda grass in the sera of nonatopic subjects and patients with inhalant allergy (at the time of initial diagnosis, following specific immunotherapy was investigated with an enzyme immunoassay. The intra-assay and inter-assay coefficients of variation for this assay ranged from 1.74%-4.62% and 3.18%-9.12%, respectively. IgG antibodies were found in the sera of the majority of nonatopic and all of atopic subjects. The differences in the concentration of these antibodies between these three groups were statistically significant (P less than 0.001). Specific immunotherapy resulted in a rise in the serum levels of allergen-specific IgG antibodies and, following an initial period of modest increase, a decrease in the level of allergen-specific IgE antibodies. Specific IgG response correlated with both the cumulative antigen dose and the clinical benefit that accrued from specific immunotherapy (P less than 0.001). The increase in the serum concentration of specific IgG was most pronounced in patients with high RAST scores at the time of initial diagnosis (P less than 0.001). The concentrations of short-ragweed specific IgG antibodies assayed with multiple samples in three patients with ragweed hay fever appeared not to be affected by the short-ragweed season to any significant degree. We conclude that direct enzyme immunoassay for allergen-specific IgE and IgG antibodies are useful in vitro monitors of immunologic responses to specific immunotherapy for inhalant allergy.