The analogs of adenosine D- and L-phenylisopropyladenosine (D- and L-PIA) and chloroadenosine (CADO) induced analgesia in mice (hot-plate test). 2. The antinociceptive effects of the three adenosine agonists were antagonized by caffeine but were unaffected by naloxone. 3. Morphine-induced antinociception was increased by pretreatment with adenosine agonists. 4. Whereas CADO significantly attenuated the induction of morphine tolerance, D- and L-PIA did not affect the process.