Plasminogen activators (PAs) proteolytically convert plasminogen to plasmin, which, in turn, can degrade most proteins. This system has been implicated in a variety of biological processes. Using immunocytochemical methods, we here describe the localization of tissue-type PA (t-PA) in rat somatostatin cells. In the pancreatic islets, a low number of strongly t-PA-immunoreactive cells was found. By sequential staining, we found these cells to constitute a subpopulation of the somatostatin cells. Biochemical analysis of extracts from isolated rat islets demonstrated the presence of t-PA, and immunoblotting analysis demonstrated one band with a similar electrophoretic mobility. No urokinase-type PA immunoreactivity was found in the rat endocrine pancreas. A granular t-PA immunoreactivity resembling that found in adjacent sections with somatostatin antiserum was found in the median eminence of the hypothalamus. No t-PA immunoreactivity could be detected in somatostatin cells of the gastric and intestinal mucosa.