The effects of fish oil and naloxone on blood pressure, catecholamines, and endorphins during the cold pressor test were evaluated in a randomized, double‐blind, placebo‐controlled, two‐way crossover trial of normotensive and medication‐free hypertensive men (n= 13 each). Subjects were given 5 gm ω‐3 fatty acids per day or placebo for 30 days with a 1‐month washout between interventions. The cold pressor test (hand in ice water for 5 minutes) was done at the end of the treatment periods. Intravenous naloxone (10 mg) or placebo was given before the cold pressor test. Fish oil‐treated, normotensive, or hypertensive groups had similar changes in blood pressure, plasma catecholamine levels, and β‐endorphins during the cold pressor test, but naloxone treatment was associated with fivefold and tenfold increases in plasma epinephrine and Cortisol levels, respectively. Naloxone may modulate sympathomedullary discharge through blockade of endorphin activity. It is unlikely that endorphins are involved in the blood pressure increase during the cold pressor test or that fish oil alters this response.Clinical Pharmacology and Therapeutics(1991)50,538–546; doi:1