The most important neuroendocrine response to stress is an increase in plasma epinephrine concentration. To investigate the clinical significance of this response, plasma catecholamine levels were measured (single-isotope derivative assay) in chronic stress (severe illness; n = 22) and acute maximal stress (cardiac arrest; n = 23). The results were then compared with the values from 60 normal resting subjects: epinephrine (mean ± SEM) 0.034 ± 0.002 ng/ml; norepinephrine 0.228 ± 0.01 ng/ml. Chronic stress (intensive care unit patients) was associated with a fourfold elevation of epinephrine concentration (0.14 ± 0.06 ng/ml; range 0.01 to 1.37; p < 0.01 versus normal control subjects). Acute maximal stress (resuscitation following cardiac arrest) resulted in a greater than 300-fold increase in the plasma epinephrine level (10.3 ± 2.9 ng/ml; range 0.36 to 35.9; n = 15; p < 0.01). Peak plasma epinephrine levels in successfully resuscitated patients (n = 6) ranged from 0.36 to 273 ng/ml (three patients had received epinephrine therapy). The plasma norepinephrine level was increased twofold in intensive care unit patients (0.52 ± 0.06 ng/ml; p < 0.01) and 32-fold after cardiac arrest (7.37 ± 1.8 ng/ml; p < 0.01). During resuscitation, the correlation between the simultaneous epinephrine and norepinephrine levels was highly significant: r = 0.76; p < 0.01. It is concluded that (1) chronic, severe stress produces only moderate elevations of plasma epinephrine levels (up to 1.37 ng/ml), whereas acute stress produces marked increases of plasma epinephrine that may reach the extraordinarily high level of 35.9 ng/ml, (2) the potential toxicity from the adrenomedullary response to acute stress is further exacerbated by the parallel release of norepinephrine, and (3) under close medical monitoring, it is possible to survive with plasma epinephrine concentrations as high as 273 ng/ml.