1 A study has been made of the action of adenosine on surface slices of guinea-pig olfactory cortex in vitro. 2 With extracellular recordings from the pial surface and stimulation of the presynaptic input, the lateral olfactory tract (LOT) generated a monosynaptic negative wave representing dendritic excitatory potentials. This negative wave was depressed by bath application of 1 micron adenosine with increasing effect up to 1 mM. Adenosine 5'--triphosphate (ATP), adenosine 5'-monophosphate (AMP) and cyclic adenosine 3',5'-monophosphate (cyclic AMP) had similar depressant actions. Adenine and guanosine were very weak depressants. 3 Theophylline concentrations in the range 10 micron to 3 mM progressively antagonized the action of adenosine. 4 Dibuyryl cyclic AMP (100 micron) and agents which increase intracellular cyclic AMP were not depressants, suggesting that the action of adenosine was not cyclic AMP-mediated. 5 Intracellular recordings confirmed the depressant effect of adenosine on excitatory potentials generated by LOT stimulation and also showed that postsynatpic action potentials and the membrane of the soma were unaffected by adenosine. 6 Since presynaptic action potentials were also unaffected by adenosine, these experiments suggest that adenosine reduces excitatory transmission at LOT synapses and fortifies the idea that adenosine has a 'neurohumoral' action.