In previous studies, both animals and malnourished children receiving 25% of the protein-energy intake of a control group, resulting in a 25% weight loss, had lower ratios of phosphocreatine to beta-ATP and of phosphocreatine to inorganic phosphorus, higher free ADP concentrations, and lower free energy of ATP hydrolysis than the control group. Therefore, the effect of malnutrition on muscle energetics in adult humans was examined by using 31P-nuclear magnetic resonance spectroscopy in malnourished patients with a mean body mass index (BMI; in kg/m2) of 16.4 compared with healthy control subjects with a significantly higher body mass index of 24.5 (P < 0.005). The mean (+/- SEM) ratio of phosphocreatine (PCr) to ATP in the malnourished patients was 2.28 +/- 0.27, which was significantly lower than the ratio of 3.1 +/- 0.15 in control subjects (P < 0.02). The ratio of inorganic phosphorus (Pi) to ATP in malnourished patients was 0.33 +/- 0.04, which was significantly lower than the ratio of 0.48 +/- 0.03 in control subjects (P < 0.02), but the ratio of PCr to Pi was not significantly different from that in control subjects. There was a significant correlation between BMI and the ratio of PCr to ATP (P < 0.01) and of Pi to ATP (P < 0.01). These data suggest that progressive loss of BMI is associated with a relative loss of muscle creatine and phosphorus in relation to ATP. The findings were unlikely to have been due only to atrophy of fast-twitch fibers because such atrophy would have altered the ratio of PCr to Pi.