The double-port infusion protocol during adenosine thallium imaging involves the use of two infusion systems, one for adenosine and one for thallium. The single-port infusion protocol, on the other hand, uses one infusion system; both adenosine and thallium are injected via a "Y" connection. This study examined the possibility that the single infusion system, by displacing a column of blood filled with adenosine, may be responsible for a greater incidence of side effects. In a parallel study, 140 patients underwent adenosine thallium imaging with the single-port system (group 1) and 140 patients underwent imaging with the double-port system (group 2). Both groups were comparable in age (67 ± 10 years vs 64 ± 11 years), gender (men comprised 56% of patients in group 1 and 64% in group 2), resting heart rate, and systolic blood pressure. More patients in group 1 had chest pains (57% vs 44%; p = 0.03), ST-segment depression (25% vs 9%; p = 0.005), nausea (11% vs 4%; p = 0.04), and second- or third-degree atrioventricular block (11% vs 5%; p < 0.08) than did patients in group 2. The other side effects were similar, and peak heart rate and peak systolic blood pressure were also similar. The thallium images that used single-photon emission computed tomography were abnormal in 61% of patients in group 1 and in 65% of patients in group 2 (p = not significant). The images were of high quality in all but two patients, both in group 1, who had poor images because of low counts, possibly because of backflow of thallium into the adenosine infusion tubing. Thus the use of a single-port infusion system during adenosine thallium imaging is associated with a greater incidence of side effects, possibly because of a bolus effect. A slower rate of thallium injection, the use of a double-lumen catheter, or preferably, the use of double-port infusion systems is suggested to decrease the number of side effects. © 1992.