The cremasteric microcirculation was studied in rats exposed to chronic hypoxia. Control male weanling Sprague-Dawley rats (n = 8) were raised for 42-49 days at 752 mmHg. Hypoxic rats (n = 9) were reared for 3 days at 551 mmHg, 4 days at 461 mmHg, 3 days at 371 mmHg, and 31-38 days at 311 mmHg (6,000 m). Red blood cells labeled with fluorescein isothiocyanate were injected. The exposed cremaster was observed using fluorescence microscopy. Rats acutely breathed 10, 21, and 30% O2 spontaneously in random order. Hypoxia-adapted animals had greater (P less than 0.01) red cell flux (10.6 +/- 1.0 vs. 5.7 +/- 0.4/s), capillary hematocrits, capillary-to-systemic hematocrit ratios (0.42 +/- 0.02 vs. 0.33 +/- 0.02), and reduced red cell spacing (11.4 +/- 1.3 vs. 22.3 +/- 2.0 microns) than controls under 21% O2. Chronically hypoxic rats also demonstrated significantly (P less than 0.05) larger capillary diameters (6.52 +/- 0.04 vs. 6.15 +/- 0.06 microns) and greater perfused (135 +/- 5 vs. 94 +/- 3 mm/mm3) and anatomic (182 +/- 5 vs. 151 +/- 8 mm/mm3) microvessel length-densities at 21% O2. Results were generally similar for 10 and 30% O2. Bulk capillary blood flow was significantly (P less than 0.01) greater in controls (2.75 +/- 0.32 vs. 1.87 +/- 0.12 pl/s) only under 30% O2. Our experiments demonstrate that numerous physiological, in addition to anatomic, alterations can occur in the cremasteric microcirculation in response to chronic hypoxia.