Goat antibodies developed against pure rabbit pulmonary an iotensin-converting enzyme (pe tidyl dipeptidase, EC 3.4.1) were administered intravenousyto rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states. Angiotensin-converting enzyme (EC 3.4.15.1) is a COOHterminal peptidyl dipeptidase that catalyzes release of His-Leu from angiotensin I (1) to yield angiotensin II, the biologically active vasopressor octapeptide of the renin-angiotensin system (2, 3). It also liberates Phe-Arg and Ser-Pro from bradykinin (4, 5), thereby inactivating this vasodepressor nonapeptide. The enzyme is a glycoprotein (5, 6) that is localized on the luminal surface of vascular endothelial cells in anatomic juxtaposition to the circulation (7)(8)(9). Specific chemical inhibitors of its activity (10-12) can reverse experimental renovascular hypertension (13-17) and can reduce blood pressure in a substantial fraction of human hypertensive disease (18, 19). These considerations suggest that converting enzyme provides an unusual opportunity for exploring the possibility that the activity of an enzyme can be inhibited by specific anticatalytic antibody in vivo and that a pathologic process can thus be immunologically controlled.To investigate this possibility we isolated pure rabbit pulmonary converting enzyme (5, 6) and then developed goat antibodies against it (20). When these antibodies were administered intravenously to rabbits, even in relatively small amounts, they caused an immune-dependent lethal reaction that could not be explained solely on the basis of their anticatalytic effect (21 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisenmnt" in accordance with 18 U. S. C. §1734 solely to indicate this fact.In order to circumvent this lethal reaction we examined immunologic homology of the rabbit enzyme with enzymes from other species by using the antibodies to rabbit enzyme as a probe (24). We found that these antibodies inhibited rat converting activity in vitro and were well tolerated by this heterologous recipient animal even at very high dosage. It has not yet been established whether the lethal effect in rabbits as contrasted with rats is a universal complication of administration of antibody to converting enzyme to homologous recipient animals or a species-specific phenomenon associated with the rabbit. The recent isolation of pure canine converting enzyme and goat antibodies directed against it (25) provides another experimental system ...