Patients undergoing surgical procedures using sodium nitroprusside‐induced hypotension were studied to determine the role of the renin‐angiotensin system in the pathogenesis of rebound hypertension (RH) after discontinuing sodium nitroprusside (SNP) infusion. Retrospective observations documented RH in 9 of 12 patients (group I) with a systolic blood pressure (SBP) increase from 112 ± 3.92 before SNP to 144 ± 5.60 torr 10 min after SNP (p<0.001). In 12 patients (group II), plasma renin activity (PRA) rose from 950 ± 432 to 3,611 ± 1,874 pg/ml/hr (p<0.0005) during SNP and remained elevated (2,504 ± 792 pg/ml/hr) 30 min after cessation of SNP. SBP rose from a control (pre‐SNP) value of 112 ± 5.24 to 129 ± 8.52 torr after discontinuation of SNP (p<0.05). Significant PRA and SBP changes did not occur in a matched group of patients (group III) who did not receive SNP. That RH after cessation of SNP infusion was associated with persistent elevation of PRA leads us to suggest that RH may be attributable to the unopposed effects of the renin‐angiotensin system after the rapid plasma disappearance of SNP.Clinical Pharmacology and Therapeutics(1980)27,32–36; doi:10