A general method applicable for the determination of any mammalian tissue's proliferative pattern is described. This method determines the cellular mRNA level of a proliferation-dependent gene, histone H3, by in situ hybridization. The cell-cycle S-phase-specific expression of this highly conserved ubiquitous cellular gene, and the lack of it in resting cells, permits the unambiguous identification of cycling cells in any tissues, normal or diseased. This method can be conveniently coupled with routine biopsy and could be streamlined for a central laboratory with results obtainable in 2 days. Furthermore, this procedure works successfully on formalin-fixed paraffin-embedded sections, thus allowing retrospective studies of biopsies or autopsy materials.