In order to understand mechanisms underlying variability of IgE-mediated responses in vivo, we compared effects of different monoclonal antibodies of IgE on dermal and airway responses in a group of atopic dogs. Using intradermal testing, fourteen antibodies were screened in Basenji-Greyhound dogs. For further comparisons between dermal and airway responses, we selected the two antibodies that stimulated the greatest and least dermal responses, respectively. These antibodies bound to IgE with similar affinities (4.1 +/- 0.2 x 10(9) and 1.5 +/- 0.2 x 10(10) M-1). Dose-response curves to intradermal testing were constructed for these two antibodies. On a separate occasion, peripheral airway resistance (Rp) was determined before and after aerosol challenge with an antibody or saline in the same dogs. For one antibody (affinity 4.1 +/- 0.2 x 10(9) M-1), Rp reached a maximum (407 +/- 142% above baseline; mean +/- SE, n = 6) 10 to 15 min after challenge, while maximum responses to saline (62 +/- 16% above baseline, p < 0.01) occurred immediately after aerosol delivery. Responses to the other antibody were similar (p = 0.068) to responses to saline. The magnitude of skin responses did not predict the magnitude of airway responses. These findings suggest that differences in affinities, alone, do not predict magnitude of responsiveness to the anti-IgE antibody and that mechanisms underlying skin and airway responses may differ qualitatively and/or quantitatively.