OBJECTIVE: The calcium antagonist nisoldipine has recently been reported to induce rather than to attenuate ischaemia in some patients with stable angina. The aim of the study was to investigate the mechanisms underlying this proischaemic effect. METHODS: In 20 anaesthetised dogs systemic haemodynamic variables, regional myocardial blood flow (coloured microspheres), and systolic wall thickening (sonomicrometry) were measured during control conditions and following severe stenosis on the left circumflex coronary artery, before and after intravenous administration of equihypotensive doses of either nisoldipine (group I, n = 10) or dipyridamole (group II, n = 10). Finally, measurements were performed while the drug induced decreases in mean aortic pressure--18 (SD 6) mmHg in group I and 14(6) mm Hg in group II--were reversed by inflation of an intra-aortic balloon. RESULTS: The stenosis decreased posterior wall thickening to 50% of control, and posterior subendocardial blood flow from 1.48(0.27) to 0.61(0.19) ml.min-1.g-1 in group I and from 1.49(0.23) to 0.62(0.18) ml.min-1.g-1 in group II. Subendocardial blood flow was further decreased after administration of either nisoldipine [0.37(0.20) ml.min-1.g-1, p < 0.05 v stenosis] or dipyridamole [0.22(0.11) ml.min-1.g-1, p < 0.05 v stenosis]. Regional myocardial blood flow in the anterior region was increased. The drug induced reduction of subendocardial blood flow decreased posterior wall thickening further from 9.3(2.1) to 6.2(3.9)% (p < 0.05 v stenosis, group I) and from 9.1(1.7) to 4.3(2.4)% (p < 0.05 v stenosis, group II). When the drug induced decrease in aortic pressure was reversed, subendocardial blood flow again increased in group I [0.63(0.19) ml.min-1.g-1, p < 0.05 v stenosis and nisoldipine] whereas in group II it remained decreased [0.40(0.29) ml.min-1.g-1, NS v stenosis and dipyridamole]. There was restoration of posterior wall thickening in group I [10.4(3.8)%, p < 0.05 v stenosis and nisoldipine], but not in group II [5.2(3.5)%, NS v stenosis and dipyridamole]. CONCLUSIONS: Nisoldipine and dipyridamole decrease subendocardial blood flow and contractile function distal to a severe stenosis when aortic pressure is decreased. No aggravation of ischaemia by nisoldipine is seen when hypotension is prevented. In contrast, dipyridamole in the absence of hypotension still induces a redistribution of flow at the expense of the ischaemic region.