The effects of delta-9-tetrahydrocannabinol on sensory activity in the thalamic intralaminar nuclei, centralis lateralis and the mesencephalic reticular formation were compared with the effects on cortical association or heterosensory systems in alpha-chloralose-anesthetized cats. The drug depressed the anterior marginal responses to multiple-modality sensory stimulation 30 min after administration of 2 mg/kg. Posterior suprasylvian responses were not significantly depressed except during 15 min postadministration. The drug did not depress sensory responses at the centralis lateralis or the mesencephalic reticular formation. Cortical responses evoked by stimulation of the latter were globally depressed by the drug. In contrast, delta-9-tetrahydrocannabinol depressed the anterior marginal response to centralis lateralis stimulation and not the posterior suprasylvian response similarly to the responses to sensory stimulation. The drug was without effect on caudate nucleus responses to stimulation of the mesencephalic reticular formation or centralis lateralis. These data demonstrate that, unlike pentobarbital, delta-9-tetrahydrocannabinol maintains heterosensory afferent activity to mesencephalic and thalamic sites and that its unique properties appear to be due, in part, to the selective disruption of heterosensory thalamocortical function.