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The size and shape of growth hormone (GH)-producing rat (type II)-somatotrophs was studied during secretory stimulation by either human GH-releasing hormone (hGHRH(1-29)) or 50 nM extracellular potassium. A new type of perfusion chamber for light microscopy allowed the interpretation of early changes in cell morphology. The exposure to 10 nM hGHRH caused a significant transient decrease in cell volume to 94.4 +/- 2.1% within 2 s. The cell volume recovered to 99.2 +/- 1.3% at 30 s. A second, more gradual volume decrease then followed (60 s), which stabilized at about 92.5 (8 min) and was still present after 20 min of continuous hGHRH exposure. Potassium, 50 mM, gave an immediate and persistent cell volume increase of about 5%. The fluctuation in rat somatotroph volume after hGHRH exposure correlates to a previously observed biphasic GH-secretory pattern involving an initial burst secretion and a second slow phase secretion. The transient early volume decrease may reflect ion fluxes across the membrane and/or the response of the cytoskeleton to calcium mobilization during the GH-secretory onset. The second, persistent, volume decrease closely correlates to the calculated volume of lost GH vesicles.