Cortical and striatal regions of the brain contain high levels of the cannabinoid‐1 (CB1) receptor, the central neuronal mediator of activity‐dependent synaptic plasticity evoked by endocannabinoids. The expression levels of parvalbumin, a calcium‐binding protein found in fast‐spiking interneurons of both regions, may be controlled in part by synaptic activity during critical periods of development. However, there is currently no evidence that CB1 receptor expression affects parvalbumin levels in either cortical or striatal interneurons. To assess this possibility, we examined parvalbumin immunoreactivity in the dorsolateral striatum, primary motor cortex (M1), and prefrontal cortex (PFC) of CB1 knockout and wild‐type C57/BL6 mice. Quantitative densitometry showed a significant decrease in parvalbumin immunoreactivity within individual neurons in each of these regions of CB1 knockout mice relative to controls. A significantly lower density (number of cells per unit area) of parvalbumin‐labeled neurons was observed in the striatum, but not the cortical regions of CB1 knockout mice. These findings suggest that CB1 receptor deletion may elicit a compensatory mechanism for network homeostasis affecting parvalbumin‐containing cortical and striatal interneurons. Synapse, 2011. Published 2011 Wiley‐Liss, Inc.