Of 32 studies comparing plasma norepinephrine concentrations in hypertensive and normotensive groups, 28 (88%) reported higher levels in the hypertensive group. However, only 13 (41%) of the studies reported statistically significant hypertensive-normotensive differences in norepinephrine, leading the present attempt to identify factors differentiating "positive" studies (those reporting significant hypertensive-normotensive differences) from "negative" studies (those reporting nonsignificant differences). Hypertensive norepinephrine levels were similar in positive and negative studies (281 vs 288 pg/ml), but normotensive levels were lower in the positive studies (177 vs 269 pg/ml). When compared with the fluorimetric technique, the radioenzymatic type of assay was associated both with a lower frequency of positive results (25% vs 100%) and greater intrastudy standard deviations (152 vs 72 pg/ml). Hypertensive-normotensive differences varied inversely with age (r = -0.37). Resolution of the persisting controversy about norepinephrine levels in essential hypertension will require more attention to the causes of variability associated with the assay technique, to the sources, characteristics, and treatment of the normotensive controls, and to the age of the patient population.