Does ethanol affect the adrenergic response to trauma? In 52 trauma victims, grouped according to blood ethanol concentrations, we found there was a significantly higher mean plasma norepinephrine (NE) concentration in heavy imbibers than in those with no detectable blood ethanol (790 ± 84 pg/ml vs. 1,260 ± 310; p=0.02). To control confounding variables such as intensity of pain, injury severity, etc., we selected blood loss (0.9% body weight over 15 min), as an aspect of trauma to study in six normal subjects before and after ingestion of 6 oz and 10 oz of 86-proof liquor on successive days. As expected, the increase in plasma NE upon assumption of an upright position was accentuated by blood loss, (384 ± 43 pg/ml prebleed; 694 ±16 post-bleed; p=0.001). The postural or hypovolemic effect on plasma NE was enhanced by ingestion of ethanol at 6 oz prebleed (529 ± 42 pg/ml pre-ethanol vs. 732 ± 64 post ethanol; p=0.02) or at 10 oz post-bleed (694 ± 16 pg/ml vs. 1,154 ± 166; p=0.04). There was an approximate dose-response effect of ethanol on plasma NE under all conditions; for example, post-bleeding upright NE: 717 ± 57, no ethanol; 1,045 ± 221, 6 oz ethanol, and 1,257 ± 182, 10 oz ethanol. Plasma epinephrine concentrations were not significantly affected by positional changes, blood loss, or ethanol consumption. Standing systolic blood pressure (BP) fell (139 ± 71 mm Hg vs. 113 ± l l; p=0.02) as did diastolic BP (98 ± 8 vs. 79 ± 11; p=0.03) after blood loss, but ethanol ingestion did not modify the BP decrease in spite of increased plasma NE. We conclude that ethanol ingestion has a significant enhancing effect on the plasma NE response to hemorrhage. The blunting effect by the ethanol on NE vascular response may moderate the impact of adrenergic stimulation.