Recently, there has been increasing interest in adenosine as a mediator of allergic asthma. Adenosine causes a rapid and profound bmnchoconstriction in allergic, but not in normal rabbits (All, et al. FASEB J. 3_,1236, 1989). The rabbit model for late phase asthma has physiologic characteristics and pharmacologic sensitivity comparable to human asthma. In the present study, we estimated the contribution of the adenosine A~ vs. A~ receptor in the allergic rabbit lung using 5' N-ethylcarboxamide adenosine (NECA) and cyclopentyl adenosine (CPA) as an A2 and A~ agoniet respectively. Analogs of adenosine were given by aerosol to compare relative potency of each in causing bronchoconstriction. Neonates were immunized with ragweed to preferentially produce specific IgE and develop non-specific bronchial hyperresponsiveness (PC~o histamine). Four allergic rabbits (PC~o histamine 4.49 +_ 0.31 mg/ml) were challenged with adenosine and its analogs and PCso was determined. NECA and CPA were given three days apart followed by a histamine chaltenge to determine change in airway hyperresponsiveness. The PC~o (mg/ml) values for adenosine, NECA, and CPA in these animals were 9.85 +_ 0.86, 3.90 + 0.27 (P < 0.002), and 1.45 _+ 0.26 (P < 0.001), respectively (PCso for CPA vs NECA P < 0.002). There was no significant change in the baseline airway reactivity 24 hrs. following adenosine or either of its analogs. These data suggest that adenosineinduced bronchoconstriction in this model is mediated primarily through activation of an A 1 adenosine receptor.