A B S T R A C T Using His btundle recording techniq(utes, we examined direct and auitonomically mediated condtuction system effects of (qtiinidine in five cardiac transplant recipients who have anatomically denervated hearts. We made control conduction interval and refractory period measurements, and then inftused 10 mg/kg quiinidine gltuconate over a 20-min period. At 30 min, we determined the electrophysiologic changes indtuced by quiinidine. Quiinidine significantly increased the atrial-His (AH) interval (from 97±9 [SEM] to 1083+7 ms,P < 0.001), the His-ventricular (HV) interval (from 43.9± Ito 52.8±3 ms, P < 0.01), the donor heart sintus cycle length (from 599±38 to 630 ±56 ms, P < 0.08), and the atrial effective refractory period (from 214 ± 14 to 241 ± 11 ms, P < 0.01). Qtuinidine significantly decreased the innervated, remnant atrial sintus cycle length (from 847±104 to 660±96 ms, P < 0.01) and the blood pressure. The mean plasma concentration of qutiinidine at the time that electrophysiologic measturements were repeated was 4.37+0.449 ,ug/ml. We concltude that quiinidine's predominant sintus nodal and atrioventrictular nodal effects in man are auitonomically mediated and opposite to its direct actions upon these structures. On the other hand, quinidine's prevailing effect on atrial refractoriness and His-Purkinje conduction in man is direct.