leishmania histone h1 overexpression delays parasite cellcycle progression parasite differentiation and reduces leishmania infectivity in vivo episomal expression of leishmania histone h1 sense mrnas in leishmania major promastigotes was found previously to result in overexpression of this molecule and to reduce parasite infectivity in vitro herein we evaluated the in vivo infectivity of these transfectants in balbc mice and showed that it is dramatically reduced no lesions were observed in this group of mice and this was associated with an extremely low number of parasites both in the footpad and in the draining lymph nodes interestingly the transfectantsreduced infectivity was associated with a delay in their cellcycle progression and differentiation to axenic amastigotes assessed in vitro therefore the dramatic reduction in their infectivity may be attributed to the abovementioned phenotypic modifications as the metazoan linker histone h10 homologue is known to delay cellcycle progression in mammalian cells we investigated whether its leishmania counterpart which possesses homology to its cterminal region when expressed in mammalian cells may also affect their cellcycle progression it was thus shown that leishmania histone h1 expressed in cos7 and nih 3t3 cells delays cellcycle progression in these cells too the latter strengthens the phenotype observed in leishmania and provides evidence that critical functions of histone h1 molecules are conserved throughout evolution