The adenosine A1 receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) has been administered systemically to rats together with the neurotoxin kainic acid. At the lower doses of CPX tested, 10 and 50 micrograms/kg, which were sufficient to prevent the neuroprotective activity of exogenous agonists, there was no exacerbation of the neuronal damage. At 250 micrograms/kg, some enhancement of damage was found, which was also produced by 8-(p-sulphophenyl)theophylline, a non-selective xanthine which does not cross the blood-brain barrier. The results are consistent with the involvement of a central A1 receptor in the neuroprotective activity of purines, and suggest that blockade of a peripheral adenosine receptor, possibly of the A2 type, may increase neuronal damage.