The present research aimed at investigating the opioid-adenosine interaction on regional cerebral blood flow (rCBF). Therefore rCBF in the sensory cortex of morphine-naive and -dependent rats was measured using the laser-Doppler flowmetry technique. The results showed that adenosine (10(-5), 10(-4), 10(-3) M) significantly increased rCBF in morphine-dependent rats (MDR) (P < 0.01). This effect was inhibited by theophylline (5 x 10(-5) M). Also systemic naloxone (0.5, 1.5 and 3 mg/kg, s.c.) significantly increased rCBF in MDR and it was accompanied by elevated blood pressure and heart rate. Local adenosine (10(-4) M) significantly augmented naloxone (0.5 mg/kg)-induced increase in rCBF of MDR but had no significant effect on naloxone's (1.5 and 3 mg/kg) increasing effect on rCBF. Theophylline also has no effect on naloxone increasing effect on rCBF. These data suggest that adenosine receptors responsiveness increase in sensory cortex of MDR. Naloxone also highly increased rCBF of MDR that probably not interfere with adenosine receptors. Also, it seems that adenosine acts as a modulator in rCBF regulation of morphine-dependent and morphine withdrawal rats.