The specificity of nucleolar DNA organization into loops in normal and activated to proliferation human lymphocytes has been studied using two different procedures of DNA loop excision. In the activated lymphocytes the nucleolar genes were found to be organized into loops of the same size as the size of individual rDNA repeat. The loops could be excised from the genome by DNA cleavage at matrix attachment sites with either the endogenous topoisomerase II or an exogenous nuclease Bal 31. In normal lymphocytes none of these enzymes generated any specific pattern of nucleolar gene long-range fragmentation, indicating that proliferation arrest correlates with a certain reorganization at higher orders of DNA packaging.