Hypokinetic/hypodynamic and antiorthostatic responses to weightlessness and bedrest were simulated in mice using a suspension technique. Animals were suspended for 1 or 2 weeks in an antiorthostatic posture and positioned to permit freedom of movement but eliminate load bearing by the hindlimbs. Suspended mice exhibited reduced food and water intakes and rapid 10% decrease in body weight to a level which was maintained for the remainder of the suspension period. Diuresis was evident in suspended mice, but the natriuresis and kaliuresis previously observed in the suspended rat were not evident. Differential hindlimb muscle atrophy (soleus greater than plantaris = gastrocnemius greater than EDL) and increased excretion of urea and ammonia were also noted in suspended mice. Postsuspension recovery studies indicated that the recovery process was highly effective. These results document specific responses to hypokinesia/hypodynamia and antiorthostasis in the mouse and demonstrate similarities in the responses of mice and rats to suspension. These studies expand the utility of the suspension model and suggest that the mouse may be useful in future studies simulating both weightlessness and bedrest.