Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, 125I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosis had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p < 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p < 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p < 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantification of results, and autoradiographs may be stored indefinitely for later comparison.