ISMARA - The Integrated System for Motif Actitivity Response Analysis is an online tool that models genome-wide expression or ChIP-seq data, in terms of computationally predicted regulatory sites for transcription factors (TFs) and micro-RNAs (miRNAs). The only input required for running ISMARA is either expression data (microarray CEL files or RNA-seq FASTQ and BED/BAM/SAM alignment files), or ChIP-seq data (FASTQ and BED/BAM/SAM alignment files), from a set of biological samples. Using the given gene expression or chromatin state data across a set of samples, ISMARA identifies the key transcription factors and miRNAs driving the observed expression/chromatin state changes, and makes detailed predictions regarding their regulatory roles. Results include, for each regulatory motif, inferred activities across the input samples, predicted genome-wide targets, enriched pathways and functional classes of genes, and direct interactions between regulators. All results are presented within interactive and easily navigable HTML pages. The full results are also available for download.