Forty‐six adult asthmatics allergic to D. pteronyssinus (Dp) participated in a 2‐year study. Thirty‐one underwent hyposensitization (HS‐group). Fifteen were treated with Dp‐extract (Dp‐group), and 16 with a similar extract modified by monomethoxypolyethylene glycol with reduced allergenicity (mPEG‐Dp‐group). Fifteen patients served as controls. Dp‐specific antibodies and histamine release from blood basophils were determined and compared with Dp‐sensitivity in lungs and skin. In addition, IgG and IgE against the major allergen Der p I were followed in a subgroup. Dp‐specific IgG, IgG., and IgG₄ increased significantly in both HS‐treated groups after 1 and 2 years (median; 2.5‐ to 11.6‐fold). IgG₄ was not induced if maintenance dose during the first year was less than 20,000 BU. Median skin sensitivity decreased 4.4‐ to 8.2‐fold after 1 year and 7.4‐ to 21.4‐fold after 2 years. Der p I specific IgG response was unrelated to the occurrence or change in IgE with the same specificity. The mPEG‐Dp‐extract tended to have less effect on skin sensitivity and immunological parameters, differences reaching statistical significance for skin sensitivity only. In the HS‐group, the decrease in bronchial sensitivity was significantly correlated to a decrease in IgE (r = 0.36), IgG¹/IgG₄ (r = 0.49), Dp‐specific histamine release (r = 0.58), and to an increase in Dp‐specific IgG, (r =−0.36) and IgG₄/IgE (r =−0.48). In patients improving clinically. Dp‐specific IgG₄/IgE increased, and median Dp‐specific IgE was reduced to 80 % compared with an increase to 150–160% seen in the unchanged or deteriorated group (P < 0.05). Findings indicate an improvement of effect, if the allergen dose is sufficient to reduce specific IgE and/or induce an IgG and especially IgG⁴ response.