The effect of a 4-min secretory stimulation with 10-6 M isoproterenol on the peripheral cytoplasmic zone of intermediate lobe cells of the rat pituitary incubated in vitro was studied. Two widths of the peripheral zone, a 450 nm zone and a 250 nm zone, were analyzed with electron-microscopical morphometry. Isoproterenol stimulation did not induce any significant effect on the number of electron-dense secretory granules contained within the 250 or the 450 nm zone. A 50% decrease was, however, noted in the number of electron-lucent granules situated in immediate association with the plasma membrane. The majority of the transection diameters of electron-dense granules in the peripheral zone of control cells fell within a range of 135-230 nm. A relative increase in the number of transections over 230 nm was noted after isoproterenol stimulation. In conclusion, isoproterenol stimulation induced a preferential release of electron-lucent granules from the peripheral cytoplasmic zone of the intermediate lobe cells, indicating that this subpopulation of granules represents the immediately releasable secretory pool of these cells. In addition, large electron-dense granules appeared in the peripheral zone during isoproterenol stimulation.