The microcirculatory anatomy of the hamster tibialis anterior muscle is based on modules (units) consisting of groups of 12-20 capillaries which run parallel to muscle fibers. The units are supplied by a common terminal arteriole and drained by a common terminal venule; a single terminal arteriole commonly supplies two microvascular units or a "unit pair." Regulation of the tibialis muscle microcirculation was investigated in pentobarbital-anesthetized hamsters using epifluorescence microscopy. We examined the patterns of capillary control in response to physiological and pharmacological stimuli including elevation of superfusate oxygen content, direct muscle stimulation, and topical application of phenylephrine. Changes in capillary perfusion were rarely manifested as responses of individual capillaries. The predominant response consisted of a coordinated change in virtually all the capillaries of a unit pair. For example, gradual elevation of superfusate PO2 resulted in simultaneous arrest or "derecruitment" of capillary flow in all capillaries of a unit pair in 37 of 43 such elements studied. In the 6 unit pairs showing atypical behavior, no more than four individual capillaries showed atypical behavior. Capillaries in 28 of 29 unit pairs were also recruited during muscle stimulation as members of a unit pair. In 18 of 21 unit pairs, exposure to topical phenylephrine resulted in simultaneous arrest of capillary flow in all capillaries of a unit pair. These data suggest that in this striated muscle, regulation of capillary perfusion is accomplished by control of capillary unit pairs. Accordingly, the patterns of interdigitation of units will ultimately determine the precision of control of tissue diffusion distance as well as oxygenation.