The possibility that mu-opioid-induced tachycardia and bradycardia could be mediated by different subtypes of the mu-receptor was studied in conscious Sprague-Dawley rats. The selective mu-receptor agonist dermorphin and its analog, TAPS (Tyr-D-Arg-Phe-sarcosine), a putative mu 1-receptor agonist, were given centrally. Tyr-D-Arg-Phe-sarcosine increased the heart rate, the response being inversely correlated to the dose (an increase of 71 +/- 22, 49 +/- 14 and 30 +/- 17 beats/min at doses of 0.3, 3 and 30 pmol, respectively). Dermorphin induced less clear changes in heart rate (maximum increase of 39 +/- 14 beats/min at the dose of 1 pmol). After treatment with the mu 1-selective antagonist naloxonazine (NAZ), TAPS 30 pmol and dermorphin 1 pmol decreased heart rate by -22 +/- 10 and -24 +/- 7 bpm, respectively. The bradycardiac effect of larger doses of dermorphin was potentiated by NAZ (from -25 +/- 8 to -97 +/- 22 bpm) but abolished by the non-selective antagonist naloxone. These data suggest that the high affinity mu 1-opioid receptors mediate tachycardic responses and mu 2-receptors mediate bradycardic responses.