The effects exposing rats to space flights of various lengths in a series of COSMOS satellites are reported based on an evaluation of plasma hormone levels and several enzyme activities in the tissues. The results after space flights are compared with those obtained from rats exposed to acute or repeated stress. Space flight induced selective morphological responses in the corticotrophs and gonadotrophs of the pituitary. Plasma levels of ACTH did not change, but plasma growth hormone and TSH levels decreased after longer space flights (>14 days), while prolactin in the plasma increased after short flights (5-7 days). Plasma corticosterone was higher after all flights. Catecholamine levels in plasma increased only after long space flights. These changes in plasma hormone levels affected the activities of enzymes involved in the amino acid metabolism of the liver and lipolysis in the adipose tissues. Norepinephrine level and catecholamine synthesizing enzyme activity in the hypothalamus did not change in flight rats. The norepinephrine content, however, decreased in several nuclei selected from the hypothalamus of flight rats. Increases in plasma insulin and glucose were noted in rats after space flight. Glucagone values in plasma remained unchanged. Comparing these results from flight rats against rats exposed to acute or repeated stress indicate that long stays in microgravity do not represent intensive stressogenic stimulus of the adrenocortical and sympathetic adrenomedullar systems, and hormone alterations observed after space flight may be due primarily to acute stressor activity resulting from a return to Earth's gravity (gravitational stress).