A period of drive in the presence of norepinephrine (NE) may be followed by the induction or acceleration of spontaneous activity. Experiments were carried out in sheep cardiac Purkinje fibers to determine whether the effects of NE on automaticity were modified during superfusion with hypoxic glucose-free Tyrode's solution and to assess the possible contribution of a-adrenergic influences on automaticity under these conditions. The following results were obtained: (1) Low concentrations of NE (10 ` and 3 X 10 7M) were able to induce automaticity after a period of drive in normal oxygenated (97% 02, 3% CO2) Tyrode's solution. (2) Superfusion with hypoxic (97% N2, 3% CO2) glucose-free Tyrode's solution enhanced NE-induced automaticity. (3) Practolol, in concentrations able to block the effects of NE in normal oxygenated solution, did not counteract the effects of NE in hypoxic glucose-free solution. (4) Yohimbine, but not prazosin, antagonized the effects of NE in hypoxic glucose-free solution. At the same concentration, yohimbine did not affect transmembrane potentials or automaticity induced by isoproterenol. It is concluded that a-adrenergic responsiveness appears to be enhanced during superfusion in vitro with hypoxic glucose-free solution, and that aadrenoceptors belonging to the a2-subtype in sheep cardiac Purkinje fibers might influence abnormal automaticity, possibly through an effect on oscillatory potentials.