The object of this study was to determine whether coronary collateral resistances were dependent on the direction of perfusion and to investigate whether a pattern of collateral growth with gradual circumflex occlusion could be discerned. In 12 dogs an Ameroid occluder was placed on the circumflex for 1 month, and six dogs for 3 months; 12 dogs served as controls. The circumflex, left anterior descending, and right coronary arteries were separately but simultaneously perfused in an isolated heart preparation in which the vasculature was maximally dilated with dipyridamole. Collateral flows were determined by measuring retrograde flows for two vessels simultaneously. The results showed that collateral flows from the right to the left coronaries in control dogs were 3.5-fold larger than when these collateral beds were perfused in the opposite direction. This difference in the 1- and 3-month Ameroid groups was approximately 20-fold. Relative to the control group, the collateral resistances from right to left coronary vessels were an average of 10-fold less in the 1- and 3-month groups, but there was no significant differences in resistance in the collaterals perfused from the left to the right. The results strongly suggest that collateral proliferation occurs in response to hypoxia rather than to a pressure gradient, and that collateral development is toward the hypoxid area.