Rat adrenals in different states of stimulation were examined by transmission electron microscopy following perfusion fixation using an in situ isolated-circulation technique. In unstimulated glands, intracortical capillaries were constricted and the cells of the cortex were pressed closely together with little development of filopodia or intercellular spaces. Glands fixed during the period of operative stress, or following a 1 hr perfusion with Adrenocorticotropic hormone (ACTH) showed that the radially orientated capillaries of the cortex were massively expanded, and the cells of both the glomerulosa and fasciculata exhibited an extensive development of filopodia on their surfaces. These filopodia extended into large intercellular spaces, where they often entered into complex relationships with filopodia from neighboring cells. The development of filopodia by cells of the adrenal cortex was also observed using scanning electron microscope techniques. In cells either incubated with ACTH in vitro or isolated from adrenals of rats treated with ACTH in vivo, the filopodia were numerous, often branched, and could reach as much as 1 micro m in length. In contrast, adrenal cells obtained from animals pretreated with cortisol were smooth surfaced. Other cell characteristics, including mitochondria, smooth endoplasmic reticulum, dense granules, and coated vesicles did not show such dramatic correlations with the state of stimulation. It is considered that the development of filopodia and intercellular space is related to secretory mechanisms in the rat adrenal cortex.