The development of chromatin immunoprecipitation assays (ChIP) as a tool to examine the interactions between nuclear proteins and DNA has enhanced essentially our understanding of the dynamic association of transcription factors and chromatin modifi ers with target DNA sequences. Still in vivo ChIP experiments of the central nervous system continue to represent a challenge given the considerable cellular and functional diversity, which makes the dissection of discrete circumscribed structures highly desirable. Tiny amounts of tissue can result, however, in insuffi cient quantities of starting material incompatible with many ChIP applications and lead to variable results. Here, we discuss the suitability of currently available ChIP protocols for in vivo ChIP experiments and present a new streamlined protocol that allows the processing of multiple samples with less time on hands.