The thymus gland and skeletal muscle are sensitive to the catabolic effects of glucocorticoids (GC). Previous studies using suspended rats demonstrated that muscle disuse atrophy resulting from hindlimb unloading was associated with an increase in glucocorticoid receptor site concentration. The objectives of the current studies were: to assess the temporal relationship between adrenal hypertrophy and thymic involution in suspended rats, to evaluate the role of positioning--antiorthostatic, (AO) vs. orthostatic (O)--in the thymic and adrenal responses, and to determine whether or thymic involution, like muscle disuse atrophy, was associated with an increase in GC receptor site concentration. The wet weight of the thymus was reduced by 50% (p less than 0.001) during 7 d of AO suspension. Suspended (AO) rats exhibited a significant (p less than 0.001) hypertrophy of the adrenal glands (33%), primarily on the initial day of suspension. Recovery for 7 d was associated with a return of thymus weight to control levels, but adrenal hypertrophy was not completely reversed. Rats suspended in an O position exhibited thymic and adrenal responses comparable to those of AO rats. Thymic involution in both AO and O rats was associated with a 20% (p less than 0.001) decrease in glucocorticoid receptor site concentration (pmol X mg-1 protein). However, when expressed relative to tissue weight, receptor site concentrations were not significantly different from control values. These results suggest a temporal correlation between adrenal hypertrophy and thymic involution in the suspended rat, but neither of these responses were dependent upon AO positioning.(ABSTRACT TRUNCATED AT 250 WORDS)