In yeast and mammalian cells, the cell cycle-dependent histone genes are typically expressed at a 15- to 35-fold higher level during S phase than during other phases of the cell cycle due to increases in both their transcription rates (three- to 17-fold) and the stabilities of their mRNAs (three to fivefold). In the protozoan trypanosomatids, most life cycle stage-specific genes are not regulated by changes in transcription rates, but are controlled entirely by post-transcriptional events. In contrast, little is known about cell cycle-dependent regulation of trypanosomatid genes. To examine cell cycle-associated expression of histone genes in a trypanosomatid, Trypanosoma cruzi epimastigotes were synchronized with hydroxyurea. The steady state levels of histone mRNAs in the G1, S and G2 phases of the cell cycle were found to vary only two- to fourfold, peaking in S phase. Nuclear run on assays showed that the histone genes are transcribed by RNA polymerase II and that their transcription rates do not increase in S phase relative to G1 and G2. Thus, during S phase of T. cruzi the increase in histone mRNA stability is about the same as in mammals and yeast, but no corresponding increase in the transcription rates of the histone genes occurs.