A selective under-condensation of the heterochromatic blocks 1qh, 9qh and 16qh was induced in normal peripheral blood lymphocyte cultures, using the DNA analogue 5-azacytidine. With 5-azacytidine at a concentration of 3.5 × 10-7 µM, phytohemagglutinin (PHA)-stimulated cultures (predominantly proliferating T lymphocytes) showed a significantly higher percentage of metaphases with under-condensation of heterochromatic blocks than pokeweed (PWM)-stimulated cultures (mainly activated B lymphocytes). When the concentration of 5-azacytidine in the culture medium was increased ten times, no significant difference was noticed between PHA- and PWM-stimulated cultures. At this higher dose, the response in PHA cultures remained the same while the response of PWM cultures increased dramatically. Thus, there is a differential in vitro relaxation of the heterochromatin condensation by 5-azacytidine, with T lymphocytes being much more sensitive than B lymphocytes.