The male-specific lethal (MSL) complex of Drosophila is responsible for the presence of a monoacetylated isoform of histone H4 (H4Ac16), found exclusively on the X chromosome of males. This particular covalent modification of histone H4 is correlated with a 2-fold enhancement of the transcription of most X-linked genes in Drosophila males, which is the basis of dosage compensation in this organism. Although widespread along the X chromosome, the MSL complex is not distributed uniformly, as can be seen by the indirect cytoimmunofluorescence staining of larval salivary-gland polytene chromosomes. This distribution pattern has been interpreted as a reflection of the tissue-specific transcriptional activity of the larval salivary gland and as an indication that the MSL complex associates with active chromatin. We have tested this hypothesis by comparing the chromosomal distribution of the complex in two different tissues. We performed this comparison by following the pattern of association of the complex at a specific site on salivary-gland chromosomes during larval development and determining whether an ectopic promoter located in a complex-devoid region of the X chromosome is able to attract the complex upon activation. Our results indicate that, in contrast to other chromatin-remodeling complexes that enhance transcription, the MSL complex targets active chromatin.