Eleven patients in hypertensive crisis were treated with iv sodium nitroprusside (SNP). In all cases, rapid clinical improvement was obtained. Nevertheless, 9 patients developed progressive resistance to the hypotensive effect of the drug. For the first 2 h, the mean infusion rate was 1.68 +/- 0.64 micrograms/kg . min. For the next 6 h, the mean infusion rate had to be increased to 3.1 +/- 1.14 micrograms/kg . min in order to maintain diastolic blood pressure below 110 mm Hg. Hemodynamic measurements demonstrated that this resistance was related to a marked rise in cardiac index without tachycardia. In the 6 patients with pulmonary edema who developed resistance to SNP, blood pressure control was obtained by fluid depletion. In the 3 patients without pulmonary edema who developed resistance to SNP, blood pressure control was obtained by iv acebutolol. The authors conclude that SNP rapidly improves critical hypertension. Progressive resistance to the hypotensive effect of the drug can occur in some cases and is related to a marked rise in cardiac index, which can be rapidly antagonized with fluid depletion or a beta-blocking agent to avoid SNP accumulation and cyanide toxicity.