To determine whether a benzodiazepine central nervous system depressant, alprazolam, inhibits sympathetic discharge during exercise stress, 11 healthy men, aged 21 to 35 years, performed symptom-limited treadmill tests before and on the third day of drug therapy (0.5 mg 3 times daily). Plasma epinephrine and norepinephrine levels were measured at rest and at 8 minutes, 11 minutes and maximal exercise. Owing to catheter malfunction during vigorous exercise, paired samples could be obtained from only 8 subjects at 8 minutes and from only 4 subjects at 11 minutes of exercise. During drug treatment, the plasma epinephrine level was lower at rest (30 +/- 4 vs 53 +/- 7 pg/ml, p less than 0.01), and at 8 minutes (60 +/- 13 vs 117 +/- 19 pg/ml, p less than 0.01), 11 minutes (120 +/- 39 vs 193 +/- 52 pg/ml, p less than 0.05), and maximal exercise (520 +/- 125 vs 970 +/- 324 pg/ml, p = 0.13). Plasma norepinephrine was unchanged at rest (452 +/- 57 vs 413 +/- 45 pg/ml) but lower at 8 minutes (730 +/- 75 vs 886 +/- 82 pg/ml, p less than 0.01), 11 minutes (1,077 +/- 197 vs 1,447 +/- 301 pg/ml, p less than 0.05) and at maximal exercise (3,453 +/- 487 vs 5,590 +/- 1,100 pg/ml, p = 0.09). Exercise duration (17 +/- 1 and 17 +/- 1 minutes) was unchanged on drug. Thus, alprazolam reduces the plasma catecholamine response to exercise stress, possibly by inhibiting centrally mediated sympathetic discharge. Blunting of sympathetic activation may be beneficial in cardiac disorders in which increased sympathetic tone is potentially deleterious.