In trypanosomes transcription occurs as large polycistronic units, with trans-splicing and polyadenylation generating each individual mRNA. There are no defined RNA polymerase II promoters and mRNA stabilisation is most likely the process controlling levels of differentially expressed mRNAs, since no selective modulation of gene activity has even been reported at the transcriptional level. Here, we show a large decrease in the transcription rates by RNA polymerases I and II when proliferative forms of Trypanosoma cruzi (epimastigotes and amastigotes) transform into non-proliferative and infective forms (trypomastigotes). We also show that these changes in transcription occur in parallel with modifications in the nuclear structure. While nuclei of proliferative forms are round, contain small amounts of peripheral heterochromatin and a large nucleolus, nuclei of trypomastigotes are elongated, the nucleolus disappears and the heterochromatin occupies most of the nuclear compartment. The decrease in the transcription parallels the nucleolus disassembly, as seen by the dispersion of nucleolar antigens. As T. cruzi cycles continuously through proliferative and infective forms, the molecular mechanisms involved in the control of nuclear organisation and chromatin remodelling can be revealed by this system.