Angiotensin II generation by angiotensin converting enzyme (ACE) is a key step in the regulation of systemic arterial pressure. Specific inhibitors of ACE are approved drugs for anti-hyper-tensive therapy. Paradoxically, plasma levels of angiotensin II are minimally lowered in chronically treated patients. Since the decapeptide angiotensin I is correctly processed in isolated heart tissue despite ACE-inhibition, alternative paths of intracardiac angiotensin II formation have been postulated (Dzau, 1988; Lindpaintner et al., 1988; Mebazaa et al., 1989; Johnston, 1990). Indeed, a 30 kDa neutral chymase (in the following called chymase I) specifically converting angiotensin I has now been purified from heart tissue and partially sequenced (Urata et al., 1990).

Using a PCR approach to clone haemopoietic secretory granule chymases, we have identified the gene encoding this enzyme (see Fig. I for details). The predicted amino acid residues of chymase I agree not only with the 25 N-terminal residues of purified human heart chymase (Urata et al., 1990), but also with the 35 N-terminal residues of human skin mast cell chymase (Schechter et al., 1990), except for two residues (Ser-7 in skin mast cell chymase and Gln-19 in heart chymase) which, however, Schechter and colleagues did not assign with certainty (Schechter et al., 1990). Furthermore, mouse mast cell protease 5 (MMCP-5), specifically expressed by connective-tissue-type mast cells (Reynolds et al., 1990), is almost identical (22 of 23 N-terminal residues) to chymase I. We conclude that the major angiotensin