Histones are released from formaldehyde-treated nuclei by DNase I digestion. CaSki cells were labeled with [3H]thymidine before fractionation, reversal of cross-links, and electrophoretic analysis as described. Histones, because of their very high lysine content, strongly labeled. Most of the histones detectable in this experiment were released from the nucleus by DNase I digestion (lane 1). Few were released by postdigestion washes (lane 2). Little histone was retained with the cross-link stabilized nuclear matrix (lane 3). The positions of histones H1 and H4 on the gel are marked with histones H2A, H2B, and H3 running between them.