We studied the determinants of kinin release into the venous effluent of rat hindquarters perfused with Krebs bicarbonate buffer. Kinin release in preparations perfused with control media (14.6 +/- 2.5-20.7 +/- 6.7 pg/15 min) was surpassed by that in preparations perfused with media containing kininase inhibitors (243 +/- 53 to 276 +/- 78 pg/15 min). Kinin release increased when purified kininogen (from 242 +/- 43 to 3,365 +/- 725 pg/15 min) or kallikrein (from 270 +/- 49 to 30,649 +/- 8,040 pg/15 min) was added to the perfusate. Conversely, kinin release fell when the kallikrein inhibitor aprotinin (from 272 +/- 58 to 122 +/- 27 pg/15 min) or soybean trypsin inhibitor (from 273 +/- 52 to 195 +/- 25 pg/15 min) was added. Both basal and kininogen-induced kinin release were attenuated in preparations perfused with media containing cycloheximide, a protein synthesis inhibitor, but kallikrein-induced kinin release was not. These data suggest that kinin release from perfused rat hindquarters reflects the activity of both the kinin-degrading and kinin-generating pathways and that the latter is sustained by a kallikrein manufactured de novo and by preexistent kininogen(s).