Creatinine is a metabolite unique to striated muscle. Measurement of 24-h urinary creatinine excretion is an established method for estimating striated muscle mass. However, accurate assessment of urinary creatinine excretion is often impractical. We investigated the hypothesis that total plasma creatinine could be used instead of urinary creatinine excretion to estimate body composition. In 24 men, plasma volume and plasma creatinine concentration were measured, and total plasma creatinine was calculated as the product of these two measurements. Other measurements included urinary creatinine excretion, total body water, and anthropometry. Total plasma creatinine correlated strongly with urinary creatinine excretion (r = 0.82) and with weight, total body water, and anthropometrically estimated lean body mass. Muscle mass could be predicted by the equation: 0.88 x total plasma creatinine (mg). To verify this relationship, total plasma creatinine was prospectively measured in four dogs, then their total striated muscle was removed and weighed. Predicted muscle mass was within +/- 3.9% (range = 0.5-10.8%) of observed muscle mass. The ability to estimate muscle mass conveniently and accurately from total plasma creatinine should prove valuable for future studies in physiology and body composition.