We have isolated cDNA clones of a member of the histone H2B protein family by differential screening of an Entamoeba invadens cDNA library with cDNA probes from vegetatively growing or encysting parasites. The cDNA clones reveal two polyadenylation sites, 26 nucleotides and 31 nucleotides downstream from the stop codon. RNA species recognized by E. invadens histone H2B clones are found at increased levels during cyst formation. Histone H2B RNA could be detected in both the poly(A)+ and poly(A)- RNA fractions, with stage-specific differences in the steady state levels of the two RNAs: trophozoites contain predominantly the poly(A)- RNA, while encysting parasites express predominantly the poly(A)+ RNA. Southern blot analysis suggests that both forms are transcribed from a single copy gene.