In the isolated guinea pig hearts suppression of endothelium-dependent (Acetylcholine, Substance P, postocclusive hyperaemia) and endothelium-independent (Sodium nitroprusside, PGE1) responses after 30 min subglobal ischaemia (reduction of coronary flow to 5%) were analysed in hearts which were not preconditioned or preconditioned by various protocols. Preconditioning consisted of single 5 min ischaemia (IP5) or single 10 min ischaemia (IP10) or double 5 min ischaemia (IP5 + 5). Thirty minutes of ischaemia followed by reperfusion reduced both endothelium-dependent and endothelium-independent responses approximately by 30-50% and slightly suppressed basal coronary flow by 10%. IP5 and IP5 + 5 protected against postischaemic suppression of responses to NaNP but not against postischaemic impairment of SP, ACh, and POH responses. The endothelium-dependent responses and postischaemic suppression of basal coronary flow were protected by IP10 only. In summary, in the isolated guinea pig heart the 30-min ischaemia impairs vasodilator responses to both endothelium-dependent and endothelium-independent agents. Ischaemic preconditioning protects both endothelial and smooth muscle cells function against this impairment, though endothelial cells require a more extensive preconditioning to put in motion protective mechanisms than smooth muscle cells do. Independent mechanisms of IP in endothelial cells and in smooth muscle cells are suggested.