Two invasive studies (invasive study I and invasive study II) showed positive effects of transcutaneous electrical nerve stimulation (TENS) in pacing-induced angina pectoris in terms of increased tolerance to pacing, improved lactate metabolism and less anginal pain. Invasive study I demonstrated a decrease in left ventricular afterload by TENS treatment as reflected by a fall in systolic blood pressure, and this fact was thought to be explained by reduced sympathetic activity since arterial levels of epinephrine and norepinephrine dropped during TENS in TENS responders. In invasive study II, the influence of naloxone on the effects of TENS in pacing-induced angina pectoris was studied in 11 patients with severe coronary artery disease. The patients were catheterized and treated with TENS on 2 occasions; one with a single intravenous (i.v.) dose of saline as placebo and one with a single i.v. dose of 50 mg naloxone, double-blind, in random order. Treatment with TENS increased tolerance to pacing (P less than 0.01 with placebo and P less than 0.01 with naloxone, respectively) and improved lactate metabolism (P less than 0.05 with placebo and P less than 0.01 with naloxone, respectively). The positive effects of TENS were thus reproducible and not reversed by single i.v. doses of naloxone. The results of this study indicate that the effects of TENS on the heart are not mediated by beta-endorphin but do not exclude activation of more short-acting opioids like delta or kappa receptor agonists (met-enkephalin and/or dynorphin) since naloxone has a low affinity for these receptors. It is also possible that non-opioid mechanisms are of importance.(ABSTRACT TRUNCATED AT 250 WORDS)