During a period of 35 weeks the night-day pattern of inbred Brown Norway female rats was changed weekly by alternating the light-dark (L-D) rhythm. After a period of 2 months, in a number of the animals, the cellular immune response was measured by means of Concanavalin A stimulation of peripheral blood (Con A) and a Popliteal Lymph Node Assay (PLNA). Serum corticosterone, plasma free fatty acids and peripheral leucocytes were determined as well. Seven months thereafter the remaining animals were sacrificed after which adrenal gland weight and spleen weight were established. Additionally, blood glucose and corticosterone were measured (corticosterone in vitro activity as well as the serum level). Both Con A and PLNA showed a significantly decreased immune response in the L-D shift stress group. Adrenal cortical activity measured in vitro as well as in vivo did not show any significant changes, neither at 2 months nor at 9 months. Therefore, the observed immunosuppressive effect of chronic light-dark shift stress can not be explained by an increased adrenal cortical activity. Other possible explanations for the effect of the light-dark shift stress on the immune response are discussed.