The effects of pre-existing collaterals (PC) and the perfusion size (PS) on the ischemia-induced collateral development were studied in a canine model. Under aseptic conditions, the dogs were instrumented with pairs of ultrasonic crystals to measure regional wall motion in the territory of the left circumflex (LCX) and left anterior descending coronary artery. A micromanometer was used to measure left ventricular (LV) pressure. Two to 3 weeks after surgery, 2 min coronary occlusion (CO) of LCX was repeated every 32 min consecutively day and night using a remote control, motor-driven hydraulic cuff occluder. Regional wall motion and LV pressure were monitored via a telemetry system in 23 dogs. The functional state of PC was estimated by the level of % reduction of regional wall motion at the end of the first 2 min CO, which ranged from -11 to -141%. PS of LCX area at risk determined by the post mortem angiograms ranged from 35 to 54% (mean +/- SEM; 44 +/- 1%) of LV. Number of CO needed for collateral development ranged from 8 to 628, and was exponentially related to the functional state of PC (r = -0.77, n = 23, p < 0.01), but not to PS (r = 0.43, n = 19, p = 0.07). These results suggest that the functional maturity of pre-existing collaterals is one of the major determinants of collateral development related to ischemic stimuli.