Seven men, ages 22 to 27 years, were subjected to a uniform regimen of physical exercises and tests over a period of 50 weeks, during which the variations of creatinine excretion, body weight, and physical performance were studied. The diets were as follows: a weighed, creatinine-containing normal diet I, containing 3170 cal., 70 gm protein and adequate quantities of minerals and vitamins, during 11 weeks; a weighed, essentially creatinine-free diet II, containing 3300 cal., 45 gm protein, greatly restricted quantities of B-complex vitamins, but otherwise adequate, over a period of 36 weeks — divided into equal periods of restriction and subsequent supplementations of thiamine, riboflavin, niacin, biotin, pteroylglutamic acid, pyridoxine, pantothenic acid and 40 gm casein; approximately equal quantities of a rehabilitation diet III, containing 250 to 350 gm of meat, during the last 3 weeks. After the fifth week of diet II, all supplements were given to 2 subjects who thus served as “controls” for a period of 7 months. Creatinine was determined in composite samples collected over 4 days each week. The creatinine excretion varied somewhat from week to week, often in a rhythmic manner, independent of the small changes of body weight in each subject. The maximum variations of the creatinine coefficient were of the order of ± 5% of each mean from all subjects during 9 weeks of diet I, and ± 3% of the mean from each of the control subjects during the first 9 weeks of diet II. These variations were minimized when the monthly averages were compared; the creatinine excretion then paralleled the rise or fall of body weight. During the first 5 weeks of diet II, the average coefficients of 6 subjects, weighting 62.0 to 77.0 kg, agreed within -1.5 to + 1.6 mg, or -6.1 to + 6.5% of the mean of 24.7 mg per kilogram per day; in the case of the seventh subject, who was fat and weighed 83.1 kg, the average coefficient was 22.2 mg. The average coefficients were in the same relative order of subjects with both diets I and II. Administration of diet II to 5 subjects resulted in gradually decreasing average creatinine coefficients and physical performance which were paralleled to some extent by development of early clinical signs and symptoms of dietary deficiency. In 2 subjects, the administration of thiamine did not increase the average creatinine excretion or the coefficient within 2 months. Complete supplementation did not immediately increase the average creatinine excretion or the coefficient, nor did it rapidly improve the physical performance. In 2 subjects, the creatinine excretion and the coefficient were not raised to that of diet I when meat, milk and 1 egg were given in addition to all supplements (a total of about 110 gm protein) during the last 2 months of diet II. The effect of the previous dietary regimen was still evident during the period of the rehabilitation diet III, both by comparison of the results with those from the control subjects and by comparison of the individual data at the end of diet period II with those of diet period I. Therefore, dietary restrictions with respect to protein and B-complex vitamins resulting in the development of deficiency symptoms may be reflected in metabolic changes associated with the formation and excretion of creatinine. These changes may persist, and are not rapidly abolished during subsequent supplementation.