The effects of d-nicotine on the responses induced by 1-isomer were studied in tracheae and bronchi isolated from guinea-pigs and rabbits. In guinea-pigs trachea 1-nicotine produced a biphasic response consisting of initial contraction and following relaxation. In other airway preparations 1-nicotine produced only contraction. 2. d-Nicotine did not produce any responses except for the case of guinea-pig trachea. d-isomer produced only relaxation and relative potency was approximately 0.44 in guinea-pig trachea. 3. Pretreatment with d-nicotine (30-300 microM) reduced concentration response curves for 1-isomer in a non-competitive manner in all preparations used in this study. 4. 1-nicotine at the concentration of 3 microns, which did not produce any response itself, reduced the concentration response curve of 1-nicotine in guinea-pig trachea. 5. Inhibition by d-nicotine or 1-nicotine (3 microM) of the concentration-response curve of 1-nicotine may be due to desensitization of nicotine receptors.