The present study was performed to characterize the interaction between two closely timed swallows, with particular attention being paid to short swallow intervals (less than 6-8 s) when the first wave is still traversing the esophagus and the effect of afferent stimulation in the form of bolus size. The contractile response of the esophagus to paired swallows (2-8 ml) over a range of swallow intervals (1.5-20 s) was studied in 13 normal humans using a 7-lumen perfused manometry catheter. At the shortest swallow intervals (less than 4 s), the first swallow wave is arrested in the striated muscle, while the second progresses normally. As swallow intervals lengthen (3-8 s), the first wave is arrested in the striated muscle, or is arrested or attenuated in the smooth muscle esophagus, but can continue for up to 3 s after initiation of the second swallow. The second wave is then arrested in the striated muscle, while beyond, a rapid or nonperistaltic low-amplitude wave occurs 3-5 s after the second swallow. At longer swallow intervals (greater than 6-8 s), the nonperistaltic second wave is replaced abruptly by a low-amplitude peristaltic wave of low velocity that traverses the entire esophagus. A larger first bolus increases the swallow interval required for this abrupt change, whereas a larger second bolus shortens the interval. The larger second bolus also increases the amplitude and decreases the velocity of the peristaltic second wave in both striated and smooth muscle portions. At swallow intervals greater than 10-15 s, two normal peristaltic waves occur. These studies demonstrate that each swallow of a closely timed pair directly affects the other. Not only does the second wave inhibit the first, but the first swallow and its wave markedly affect the second swallow wave. These interactions involve both the striated and the smooth muscle esophagus, and the latter interaction in particular is highly sensitive to afferent stimulation. This suggests that the interactions are predominantly neurogenic and have a significant central neural component.