Ischemia-reperfusion injury was investigated in terms of functional capillary density (FCD), capillary red blood cell velocity (cRBCv), and arteriolar and venular diameter after 4-h ischemia in the unanesthetized hamster skin-fold preparation. Animals in group 1 were studied by transillumination. Group 2 received a bolus injection of fluorescein isothiocyanate (FITC)-dextran (mol wt 150,000) and was studied by transillumination (zone 1) and epi-illumination (zone 2). In group 1, FCD decreased after ischemia (92% of baseline, 30 min), returning to control up to 24 h. cRBCv increased after reperfusion, being 175% of baseline at 24 h. Arterioles and venules dilated for 24 h after reperfusion. In group 2/zone 2, FCD progressively decreased to 11% of control, arteriolar dilation was inhibited, and cRBCv increased 30 min and 2 h after reperfusion. Tissue perfusion index (FCD x cRBCv) increased 158% in group 1 at 24 h, did not change in group 2/zone 1, and was 9% of control at 24 h in group 2/zone 2 (P < or = 0.05). We conclude that increased perfusion is a normal reaction to ischemia-reperfusion injury in this model, and previously observed capillary no reflow is due to FITC-dextran phototoxicity.