Immunoreactive dynorphin A-like material (ir-dyn A) in human plasma was measured by a validated radioimmunoassay. In peripheral plasma extracts mean concentrations between 20 and 40 fmol/ml were determined in volunteers and in patients with pituitary adenomas. In this latter group superimposable levels were detected three days before and during transsphenoidal microsurgery. Interestingly, ir-dyn A levels evaluated in extracts of hypothalamic-hypophysial plasma obtained during surgery, just after tumor removal, were 4-5 times higher than in peripheral plasma. Reverse-phase high performance liquid chromatography (rp-HPLC) of extracts of peripheral plasma samples revealed two immunoreactive peaks. The major form had the same retention time of dyn A-(1-32); whereas a second, more lipophilic, peak eluted later and was not further characterized. In contrast, rp-HPLC analysis of extracts of plasma collected from the suprapituitary region displayed only one peak eluting in the position of synthetic dyn A-(1-17). The presence of dyn-related peptides in hypothalamic-hypophysial plasma supports the hypothesis that they may play a part in the regulation of hypothalamic and/or pituitary functions in humans.