Microvascular reactions to increases in intravascular pressure were studied in the cremaster muscle of the anesthetized rat by enclosing the animal in an airtight box with the muscle exteriorized for observation of the microcirculation. Since the cremaster was exposed to atmospheric pressure, increasing pressure within the box produced equal increases in arterial and venous pressures. Thus, intravascular pressure was altered without affecting the pressure gradient for blood flow. Raising box pressure had no effect on respiration or heart rate and did not change the systemic activity of the sympathetic system, angiotensin II, or vasopressin. Diameters and flows were measured for first (107 ± 3 μm, mean ± SEM), second (87 ± 5), third (29 ± 2), and fourth (15 ± 2) order arterioles during increases in intravascular pressure of +10, + 20, and + 30 mm Hg. No significant changes in the diameters of first or second order arterioles were elicited when pressure was increased. However, when box pressure was increased to +10, + 20, or + 30 mm Hg, a sustained constriction occurred in third (29%, 45%, and 63%, respectively) and fourth (5%, 38%, and 57%, respectively) order arterioles. Blood flow was significantly reduced in all arterioles, and perivascular Po2was decreased adjacent to third and fourth order arterioles. Furthermore, the third order arteriole constrictor response was not abolished by local α-receptor blockade (phentolamine), indicating that it was not mediated by a local sympathetic axon reflex. Collectively, these data indicate that a potent, nonneural, pressure-dependent mechanism for vasoregulation is present in small arterioles of the cremaster. The sustained constriction in the presence of reduced blood flow and reduced periarteriolar oxygen tension indicates that the vascular response is independent of and capable of overriding flow -dependent (i.e., metabolic) control in resting skeletal muscle. The observations are compatible with the operation of a powerful myogenic mechanism in small arterioles.