THE HUMAN BODY HAS EVOLVED OVER THE MILLENNIA TO A NARROW RANGE OF ENVIRONMENTAL CONDITIONS ON EARTH. WITH THE ADVENT OF HUMAN SPACEFLIGHT WE HAVE NOW BEGUN TO UNDERSTAND THE PERVASIVE ROLE EARTH S GRAVITY (1-G) PLAYS IN REGULATING ORGAN HOMEOSTASIS. NUMEROUS FACTORS COULD INITIATE OR CONTRIBUTE TO TISSUE ADAPTATIONS THAT OCCUR DURING SPACEFLIGHT INCLUDING HEAD-WARD FLUID SHIFTS TISSUE UNLOADING PHYSICAL INACTIVITY AND ENVIRONMENTAL FACTORS OTHER THAN GRAVITY (E.G. PCO2 PO2 TEMPERATURE). WEIGHTLESSNESS IS KNOWN TO CAUSE A REDISTRIBUTION OF BODILY FLUIDS (BLOOD LYMPH ORGAN FLUIDS) AND UNLOADING (I.E. LACK OF GRAVITY PULLING ORGANS PHYSICAL MOVEMENT DURING WALKING STANDING ETC.). THE DEGREE OF INFLUENCE OF SYSTEMIC ADAPTATIONS BETWEEN BODILY FLUID REDISTRIBUTION VERSUS UNLOADING IS UNKNOWN FOR MOST TISSUES. ADDITIONALLY SPACEFLIGHT-INDUCED ADAPTATIONS IN ONE ORGAN SYSTEM MAY HAVE EFFECTS ON THE FUNCTION OF OTHER ORGANS SUCH AS DIGESTIVE DYSFUNCTION ASSOCIATED WITH SYSTEMIC INFLAMMATION. USING A RAT MODEL TO SIMULATE THE WEIGHTLESS ENVIRONMENT THE PURPOSE OF THIS PROPOSAL IS TO 1) EXAMINE THE EFFECTS OF 30-D HEAD-WARD FLUID SHIFTS AND UNLOADING ON THE STRUCTURE AND FUNCTION OF ARTERIES LYMPHATICS DIGESTIVE BONE SKELETAL MUSCLE VISUAL AND BRAIN NEURAL SYSTEMS BY CONTRASTING ADAPTATIONS INDUCED BY HEAD-DOWN UNLOADING WITH HORIZONTAL UNLOADING AND 2) TO DETERMINE WHETHER 30-D OF PARTIAL HORIZONTAL UNLOADING TO SIMULATE MOON (1/8-G) AND MARS (3/8-G) GRAVITY WILL ATTENUATE OR ABOLISH ADAPTATIONS INDUCED BY 30-D OF FULL HORIZONTAL UNLOADING. MEASUREMENTS SPECIFIC TO THE STRUCTURE AND FUNCTION OF ARTERIES LYMPHATICS DIGESTIVE BONE SKELETAL MUSCLE VISUAL AND BRAIN NEURAL SYSTEMS WILL BE MADE AS WELL AS EXAMINING THE PROTEOME OF THESE VARIOUS ORGANS THROUGH PROTEOMIC ANALYSIS. THE RESULTS WILL PROVIDE IMPORTANT AND NEW INFORMATION REGARDING WHAT ROLE IF ANY HEADWARD FLUID SHIFTS PLAY IN INDUCING TISSUE ADAPTATIONS WITH SIMULATED WEIGHTLESSNESS AND WHETHER THESE ADAPTATIONS ARE ATTENUATED OR ABOLISHED WITH PARTIAL LOADING.