1. The modulation by adenosine of GABA-activated current (I(GABA)) was studied in freshly isolated rat dorsal root ganglion (DRG) neurons using the whole-cell patch-clamp technique. 2. In most of the DRG neurons examined (68/90, 75.5%) adenosine (1-100 μM) suppressed I(GABA), while in some neurons examined, it potentiated (16/90, 17.8%) I(GABA). It exerted no effects on I(GABA) in a few cells (6/90, 6.7%). 3. Adenosine shifted the GABA concentration-response curve downward with no significant change of the EC50. The maximal response to GABA was suppressed by 29.6 + 2.6%. The adenosine-induced inhibition of I(GABA) showed no voltage dependence. 4. 8-Cyclopentyl-1,3-dimethylxanthine (DPCPX; 1 μM), a selective A1 adenosine receptor antagonist, partially reversed adenosine inhibition of I(GABA) and completely blocked N6-cyclo-hexyladenosine (CHA; an A1 adenosine receptor agonist) inhibition of I(GABA). DPCPX (1 μM) also blocked the suppression of I(GABA) by 2-chloroadenosine (CADO). CGS21680, a selective A(2A) adenosine receptor agonist, did not inhibit I(GABA) and DMPX, a selective A(2A) adenosine receptor antagonist, did not prevent adenosine inhibition of I(GABA). 5. Intracellular application of H-7 (20 μM; a protein kinase C inhibitor) reversed adenosine inhibition of I(GABA) while inclusion of cAMP (1 mM), H-9 (20 μM; and protein kinase A inhibitor) and BAPTA (10 mM; a chelator of calcium ions) in the recording pipette did not affect the depression of I(GABA) by adenosine. I(GABA) was also suppressed by internal perfusion of PMA, a protein kinase C activator. 6. The results suggest that adenosine, as a neuromodulator, exerts a modulatory effect on the GABA-induced presynaptic inhibition in primary sensory transmission.