Adenosine has a negative chronotropic effect in a number of species. The studies reported here were undertaken to characterize further the effects of adenosine using isolated perfused rabbit hearts and isolated SA node tissue. In the isolated perfused hearts (n = 9) the threshold doses for slowing by adenosine and 2-chloroadenosine, an adenosine analog, were 1 X 10(-5) M and 1 X 10(-7) M, respectively. In the isolated hearts adenosine, in addition to slowing sinus rate, also caused a change in the activation pattern of the right atrium. During adenosine infusion the earliest site of activation shifted from the SA node region to the right atria near the crista terminalis. The pacemaker shift was reversible upon washout of adenosine. The adenosine -induced shift in pacemaker could also be demonstrated using microelectrode recordings in the isolated SA node preparation that included the crista terminalis and some of the surrounding tissue. During control the activation of SA node preceded that of the crista terminalis (CT) by 44 +/- 4.1 ms (n = 11). Adenosine infusion caused an increase in cycle length and, in addition shifted the earliest site of activation from the SA node region to CT, i.e., in the presence of adenosine CT preceded SA node activation by 26.68 +/- 3.2 ms. All the effects were reversible after washout of adenosine. Adenosine also caused conduction block within the sinus node. No effect on the action potentials or on conduction in the CT was observed.(ABSTRACT TRUNCATED AT 250 WORDS)