Multiple organ failure (MOF) is accompanied by muscle wasting, but changes in body composition are frequently obscured by fluid retention (edema), mainly in superficial and visceral tissue. There is a need to assess body composition and changes in body composition in these circumstances independently of edema. A relation was sought between fat-free (lean tissue) mass [calculated from body weight and skinfold thicknesses and measured by using dual-energy X-ray absorptiometry (DXA)] and muscle thickness (measured using ultrasound at a variety of sites accessible in an unconscious supine subject) to determine which sites correlated best with lean body mass. The three best sites were midbiceps, midforearm anteriorly, and midthigh anteriorly: R2 for the simple sum of the three sites correlated with fat-free mass from skinfold thicknesses was 71.1%, and with lean tissue mass from DXA was 76.1%. Serial measurements of both muscle thickness and midupper-arm circumference in nine patients with MOF showed a complete dissociation; in all nine there was a significant negative correlation of muscle thickness with time (P < 0.05) but changes in arm circumference were random. Only one patient showed a significant negative correlation with time, seven showed no change, and one other showed a significant increase. The muscle thicknesses that correlate best with lean body mass are measured over the biceps, anterior forearm, and anterior thigh. Monitoring muscle thicknesses at these three sites identifies wasting in edematous patients as it is happening.