Treatment of animals with exogenous adrenal steroids or elevation of endogenous glucocorticoids results in a profound involution of lymphoid tissue. In rodent species, this lymphoinvolution is accompanied by lymphocyte cell death and extensive degradation of the genome prior to lymphocytolysis. In the present study, this process was investigated in the bursa of Fabricius of domestic fowl. Four-wk-old chicks were treated with a single injection of dexamethasone, and bursal regression and cell viability were monitored over a 72-h period. Following hormone treatment, DNA was extracted from bursal lymphocytes and analyzed by agarose gel electrophoresis. Dexamethasone treatment resulted in a rapid regression of bursal tissue that could be detected as soon as 6 h posttreatment, but lymphocyte viability was not altered until 24 h afterward. The DNA isolated from bursal lymphocytes of glucocorticoid-treated birds appeared to be degraded at internucleosomal sites and generated a "ladder" of discrete DNA fragments when analyzed by agarose gel electrophoresis. This form of hormone-induced cell death, referred to as programmed cell death, may play a key role in glucocorticoid-mediated immunosuppression.