The effects of the systemically administered adenosine kinase (AK) inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) on the striatal adenosine (ADO) release evoked by the excitotoxin, kainic acid (KA) were examined using rat bilateral striatal microdialysis. Local KA perfusion of one rat striatum caused a significant ipsilateral elevation of striatal ADO levels compared to basal and contralateral (artificial CSF-perfused) striatal ADO levels. KA-evoked striatal ADO release was augmented in animals receiving systemic 5'd-5IT treatment (cumulative dose of 7.5 micromol/kg, i.p.) compared with i.p. vehicle controls. In contrast, 5'd-5IT administration had no significant effect on basal or contralateral (artificial CSF-perfused) striatal ADO levels. Thus, consistent with the hypothesis of 'site and event specific' potentiation of ADO by AK inhibitors, 5'd-5IT unilaterally enhanced ADO levels in the striatum where KA-induced excitotoxic injury evoked endogenous ADO release, but not at the contralateral uninjured striatum.