The hypophysial portal vessels and anterior pituitary glands of adult male rats were surgically exposed, cannulated and infused for 1 min with saline, growth hormone-releasing factor (GH-RF), and dbcAMP. After cessation of infusion, anterior pituitary glands were collected at 1,5, 15, 30 or 60 min for electron microscopic and ultra-structural cytochemical examination. Before and after cannulation of a portal vessel a 1-ml sample of blood was collected at 1, 5, 15, 30 or 60 min from the femoral vein for RIA of growth hormone. When viewed ultrastructurally, the initial response following the infusion of GH-RF into a portal vessel was one of granule release. Emiocytic activity was observed at all time intervals studied. This response was followed 30 min later by evidence of increased protein synthesis. Significant increases in plasma GH levels were present at 1, 5, and 15 min following infusion of GH-RF but not at 30 or 60 min. Preliminary analysis of the RIA data suggests that dbcAMP was significantly more potent than GH-RF in elevating radioimmunoassayable plasma GH levels. The results suggest that similar mechanisms of synthesis and release were involved.