Intravenously administered adenosine and high-dose dipyridamole, both combined with low-level exercise stress, were compared in a head-to-head fashion using 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) single photo emission tomography (SPET) myocardial perfusion imaging. Thirty-nine consecutive patients who had undergone coronary arteriography underwent 99Tcm-MIBI (740 Mbq) SPET after dipyridamole (0.84 mg kg-1) and after adenosine (0.84 mg kg-1), both combined with low-level exercise (30 W load), and under resting conditions. Our results demonstrate that adenosine and dipyridamole combined with exercise have comparable haemodynamic effects, with a low incidence of side-effects. The time of recovery from the stress protocol was not significantly different: adenosine, 5.7 +/- 3.9 min; dipyridamole, 6.6 +/- 4.9 min. However, aminophylline was significantly (P < 0.05) more often administered to reverse side-effects using the dipyridamole protocol (36% of patients) compared with the adenosine protocol (8% of patients). The results of 99Tcm-MIBI SPET imaging were highly concordant and demonstrated a high diagnostic accuracy for identifying coronary artery disease (CAD). The sensitivity was 90% (95% confidence intervals 79-100%) with adenosine SPET and 93% (95% confidence intervals 84-100%) with dipyridamole SPET for identifying patients with CAD (i.e. luminal stenosis > 50%); their specificities were both 100% (95% confidence intervals 66-100%). The sensitivity of identifying angiographically diseased vessels was 81% (95% confidence intervals 70-92%) using adenosine SPET and 85% (95% confidence intervals 75-95%) using dipyridamole; the specificity for both stress modalities was 94% (95% confidence intervals 89-100%). The combination of exercise with adenosine and high-dose dipyridamole appears to be a feasible and safe method to alleviate some of the undesirable A1-receptor-mediated side-effects of adenosine. The choice of the pharmacological stress will depend on local expertise and availability.