Massive elimination of sequences occurs in the development of the macronucleus of hypotrichous ciliates. The surviving sequences are presumed to have functions in the macronucleus; what little is known about non-coding macronuclear sequences is reviewed. The 1.7 kbp macronuclear chromosome that carries a histone H4 gene consists primarily of non-coding DNA 5' of the histone gene. This region is shown by sequence comparison to carry several perfectly conserved sequence blocks up to 14 bp long, scattered amongst regions which have evolved greatly since the divergence of Oxytricha nova and Stylonychia lemnae. This result is consistent with the suggestion of Harper and Jahn [Harper, D. S. & Jahn, C. L. 1989. Actin, tubulin and H4 histone genes in three species of hypotrichous ciliated protozoa. Gene, 75:93-107] that this large non-coding 5' region may be involved in the transcriptional regulation of the histone H4 gene carried on the 1.7 kbp chromosome. Very little is known about transcriptional control in hypotrichs; identification of conserved non-coding sequences of orthologous hypotrich genes promises to provide clues to potential cis-acting control signals.