The extension of the flooding method for measuring the rate of protein synthesis, from animal to human tissues, has led to criticism. This is based on the observation that in human muscle, unlike animal tissues, the rate of synthesis in the fasting state measured with constant infusion is lower than that obtained with the flooding technique. Moreover, incorporation of infused tracer can be enhanced with a simultaneous flood, although an inhibition of incorporation has also been reported. Explanations for these observed discrepancies are explored. Evidence from studies in human muscle both with flooding and with a nonisotopic technique have given no indication of a stimulation of protein synthesis during flooding. It is therefore concluded that the most likely explanation for the discrepancy between methods is that changes in the isotopic enrichment of the precursor amino acid, which are minimized by the flooding procedure, are not adequately accounted for with the constant infusion method.