We assessed the sensitivity and specificity of glucagon stimulation and clonidine suppression tests in the diagnosis of pheochromocytoma in 113 hypertensive patients, 39 with and 74 without the tumor. In the glucagon stimulation test, blood was sampled 2 minutes after intravenous injection of 0.28 fimol (1 mg) glucagon, and in the clonidine suppression test, blood was sampled 3 hours after administration of oral clonidine, 130 /imol (0-3 mg)/70 kg body wt Baseline levels of catechols in antecubital venous blood were abnormal, with norepinephrine greater than 7.10 nmol/1 (1,200 pg/m), epinephrine greater than 1.51 nmol/1 (276 pg/ml), norepinephrine/dihydroxyphenylglycol (DHPG) ratio greater than 1.09, or dopa greater than 35.53 nmol/1 (7,000 pg/ml), in 30 of 39 patients with pheochromocytoma (sensitivity 77%) and 1 of 74 patients without pheochromocytoma (specificity 99%). Results of the glucagon test were abnormal (norepinephrine greater than 11.83 nmol/1 [2,000 pg/ml] or more than threefold increase from baseline) in 25 of 31 patients with pheochromocytoma (sensitivity 81%) and 0 of 72 patients without pheochromocytoma (specificity 100%). Results of the clonidine test were abnormal (after clonidine norepinephrine greater than 2.96 nmol/1 [500 pg/ml] or less than 50% decrease from baseline) in 29 of 30 patients with pheochromocytoma (sensitivity 97%) and in 7 of 30 patients without pheochromocytoma (specificity 67%). Very high baseline levels of catechols therefore indicated the presence of pheochromocytoma, but there were several false-negative results when normal levels were obtained. The glucagon test alone was highly specific but not sensitive, and the clonidine test was highly sensitive but less specific. Of 50 patients undergoing both glucagon stimulation and clonidine suppression tests, the results of at least one test were abnormal in 22 of 22 patients with pheochromocytoma (sensitivity 100%) and in 6 of 28 patients without pheochromocytoma (specificity 79%). When both tests were negative, the diagnosis could be excluded, and the results were conclusive in 80% of the patients. Combined glucagon stimulation and clonidine suppression testing is worthwhile in the diagnosis of pheochromocytoma by blood tests. (Hypertension 1991;17:733-741) P heochromocytoma (pheo) is a rare but important cause of clinical hypertension. The tumor often is curable, and if undiagnosed, it can lead to fatal complications. Because of the much greater prevalence of hypertension from other causes and the nonspecificity of symptoms and signs of pheo, the diagnosis is based on biochemical evidence of excessive release of catecholamines. 1 * 2 Diagnostic evaluation of hypertensive patients where pheo is considered often includes measurements of urinary excretion or plasma levels of catecbolamines or catecholamine metabolites. Recently, it was reported that rates of urinary excretion of norepinephrine (NE) and of its intraneuronal metab-