Atrioventricular nodal alternating Wenckebach periods ending in 5:1 atrioventricular block occurring during rapid atrial rhythms were explained by postulating the presence of block in three levels of the atrioventricular node. This pattern of conduction occurred in ten of 11 patients who either had received ouabain or verapamil (nine patients) or who had organic atrioventricular nodal disease (two patients). In contrast, this pattern of conduction occurred in only one of eight nonmedicated patients without organic atrioventricular nodal disease. The frequent association of this pattern with paroxysmal, tachycardia-dependent atrioventtricular nodal block suggested a similar, but not necessarily identical, mechanism. In conclusion, atrioventricular nodal alternating Wenckebach periods ending in 5:1 atrioventricular block, as well as paroxysmal atrioventricular nodal block, were only rarely the result of rapid atrial rates per se their occurrence indicating organic or pharmacologic effects on the atrioventricular node. Since both can be produced by carotid sinus pressure, further studies appear to be necessary to determine the role that vagal effects can have in their genesis.