Sensory systems are believed to play an important role in drug addiction, particularly in triggering craving and relapse, and it has been shown in previous studies that administration of cocaine can enhance evoked responses in the primary sensory cortex of experimental animals. Primary sensory cortex comprises a multi-layered structure to which a variety of roles have been assigned; an understanding of how cocaine affects evoked activity in these different layers may shed light on how drug-associated sensory cues gain control over behavior. The aim of the present study was to examine how cocaine affects whisker sensory responses in different layers of the primary sensory (barrel) cortex. Field potential and multi-unit activity were recorded from the cortex of anesthetized rats using 16 channel linear probes during repetitive (air puff) stimulation of the whiskers. In control conditions (under saline, i.v.), responses strongly adapted to the repeated sensory stimulation. Following an i.v. injection of cocaine (0.5 mg/kg, i.v.), this adaptation was strongly attenuated, giving each stimulus a more equal representation and weight. Attenuation of adaptation was more marked in the upper cortical layers in both field potential and multi-unit data. Indeed, in these layers, not only was adaptation attenuated but multi-unit response amplitudes under cocaine exceeded those under saline for stimuli occurring early in the train. The results extend our previous findings concerning the enhancement by cocaine of primary sensory responses. Insofar as enhanced neural responses equate to enhanced stimulus salience, the results indicate that cocaine may play a previously under-appreciated role in the formation of associations between drug and drug-related environmental cues by enhancing stimulus salience. The associative process itself may be assisted by a preferential action in the upper cortical layers, thought to be involved in learning and plasticity.