Aim To investigate whether the I/D polymorphism of angiotensin converting enzyme gene is associated with the therapeutic effect of catopril and the incidence of induced cough, and to explore the possible mechanism if there is indeed an association between them. Methods The angiotensin converting enzyme genotypes were detected in 186 patients with essential hypertension and were classified as DD, II and ID groups. All the paitents have taken catopril 25 mg Bid for 8 weeks. Except that 20 patients were lost to follow up, all the patients were visited every week to observe the change of blood pressure and the incidence of induced cough. Angiotensin converting enzyme was determined by ultraviolet spectrometry before and after treatment, and substance P was determined by radioimmunoassay. The thepapeutic effect, incidence of induced cough and the difference in angiotensin converting enzyme and substance P were compared among the three genotypes, and the possible correlation was anlyzed. Results There was no distinct difference in the blood pressures before treatment, after treatment, desending range and therapeutic effective power among the three groups (P>0.05). 68 patients presented induced cough. The angiotensin converting enzyme II genotype had an incidence of 57.1%, which was significantly higher than ID and DD genotypes (P<0.05). There was significant difference in the level of angiotensin converting enzyme before treatment among the three groups (P<0.001): DD genotype was much higher than ID and II (P<0.001); and ID genotype was much higher than II (P<0.001). The results after treatment were similar to that before treatment. The trend of the level of substance P was II>ID>DD before and after treatment, but no significant difference was found among them (P>0.05). The substance P was negatively related with angiotensin converting enzyme (r=-0.652, P<0.001). Conclusion There is no distinct conrrelation between the therapeutic effect of captopril and angiotensin converting enzyme gene I/D polymorphism. The patients of angiotensin converting enzyme II genotype have a higher incidence of induced cough after taking captopril. Low level of angiotensin converting enzyme is a key factor of the angiotensin-converting enzyme inhibitor related cough in patients with hypertension, and substance P is an important substance in the occurrence of angiotensin-converting enzyme inhibitor related cough.