Enzymes catalyzing histone acetylation and deacetylation contribute to the modulation of chromatin structure, thus playing an important role in regulating gene and genome activity. We showed that downregulation and overexpression of the maize (Zea mays) Rpd3-type hda101 histone deacetylase gene induced morphological and developmental defects. Total levels of acetylated histones and histone acetylation of both repetitive and nonrepetitive sequences were affected in hda101 transgenic mutants. However, only transcript levels of genes but not repeats were altered. In particular, hda101 transgenic mutants showed differential expression of genes involved in vegetative-to-reproductive transition, such as liguleless2 and knotted-like genes and their repressor rough sheath2, which are required for meristem initiation and maintenance. Perturbation of hda101 expression also affected histone modifications other than acetylation, including histone H3 dimethylation at Lys-4 and Lys-9 and phosphorylation at Ser-10. Our results indicate that hda101 affects gene transcription and provide evidence of its involvement in setting the histone code, thus mediating developmental programs. Possible functional differences between maize hda101 and its Arabidopsis thaliana ortholog HDA19 are discussed.