Owing to its simplicity, sensitivity and precision, the method of Lowry, Rosebrough, Farr, and Randall is the most widely used procedure for the quantitative determination of protein. Lowry and coworkers combined the use of copper, as suggested by Herriott, with the Folin phenol method, which originated from the work of Wu, to produce a more reliable and sensitive protein asssay. The principal disadvantage of this method is its lack of specificity. Many substances are now known to interfere with this method. Fortunately, few interfering substances are encountered in specific measurements, and simple methods exist for coping with most of the interfering substances. Other less serious disadvantages of the method include relatively slow reaction rates, instability of some reagents, and nonlinearity of the standard curve. In this article, the method of Lowry, et al. is reviewed in the context of a general standard laboratory procedure for the quantitative determination of protein. Emphasis is therefore given to the practical aspects encountered or likely to be encountered in using this method under a wide variety of conditions. The reaction mechanism is briefly reviewed, followed by an extensive list of those substances examined for possible interference in the method of Lowry et al. Methods or modifications designed for coping with these interfering substances, as well as the other disadvantages (slow reaction rates, reagent instability, nonlinearity) are then reviewed. Finally, the method of Lowry et al. is compared with other methods of protein analysis in the context of a standard laboratory procedure.