In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients matched by intradermal skin test titration, leukocyte histamine release, and the doses of both cat extract and methacholine required for 20% fall in FEV, were randomly assigned to one of the two treatment groups. Immunotherapy doses were increased to a maintenance dose of 4.56 Food and Drug Administration (FDA) units of Fel d I or if maintenance dose was less, to the highest tolerated dose. Before and during immunotherapy, we measured by intradermal titration the dose of cat extract, in FDA units of Fel d I equivalents, required for (1) 2+ end point (wheal diameter, ≥10 mm; erythema diameter, 20 to 30 mm) and (2) 20 mm end point (erythema diameter, 20 mm). By prick skin test, we measured (1) the dose of cat extract that produced a wheal equal in area to that produced by histamine, 1 mg/ml, (2) the doses of cat extract that produced a wheal 22 mm 2 in area, and (3) the sum of the wheal areas produced by five prick tests to 23.8, 7.1, 2.4, 0.7, and 0.2 FDA units per milliliter of Fel d I, respectively. After 1 year of treatment, in comparison to control patients, treated patients had significant increases in the ratio 1 year value/pretreatment value for the doses of cat extract required for intradermal test end points 1 and 2 ( p < 0.01), for prick test end point 1 ( p < 0.01), for end point 2 ( p = 0.015), and significant decreases in this ratio for prick test end point 3 ( p = 0.015). Treated patients also had significant increases in cat extract required for a 20% fall in FEV 1 ( p < 0.01), in IgG antibodies toward whole cat extract, Fel d I and cat albumin ( p < 0.001), and in IgE antibodies toward whole cat extract, ( p < 0.01). Thus, a decrease in skin sensitivity to cat extract demonstrated by both intradermal and prick methods occurred in patients after 1 year of immunotherapy with cat extract at a time when bronchial sensitivity to cat extract was decreased and IgG and IgE antibodies toward cat extract were increased.