The magnitudes of several pools of radioactively labeled precursors for RNA and protein synthesis were determined as a function of cell age during the division cycle of Escherichia coli 15 THU. Uracil, histidine, and methionine pools increased from low initial values for cells at birth to maxima during midcycle and then subsided again. These pools were small or nonexistent at the beginning and the end of the cycle, and their average values during the cycle were less than 4% of the total cellular radioactivity. The results are consistent with a linear pattern of growth for cells during the division cycle and provide strong evidence against exponential or bilinear growth of E. coli cells.The number and variety of studies of cell growth in Escherichia coli exceed those for any other cell type (13). Most of these studies conclude that the growth of individual cells is exponential or nearly so during the division cycle, although some appear to support bilinear growth. In almost all of these studies, however, cell length or volume was measured rather than the fundamental growth parameter, cell mass. When increase in cell mass was determined under steady-state growth conditions, as the product of cell volume and buoyant density, the results supported a linear growth model (13). A major difficulty in discriminating among the three models is that they predict only minor differences in cell size throughout the cycle; for example, maximum deviations in cell size predicted by exponential and linear cell growth models are less than 6% (9). Nevertheless, although growth patterns do not differ markedly for exponential, linear, and bilinear cell growth, these models have very different implications for the modes and mechanisms of the regulation of growth during the division cycle.During cell growth, nutrients and growth factors are transported into the cell with or without modification and accumulate in pools of soluble precursors or further chemical intermediates available for macromolecular synthesis. The average amount of soluble material in these anabolic pools in exponentially growing cultures of E. coli has been estimated to be less than 4% of the cell dry weight (8), so most of the dry weight of the cell is macromolecular. For this reason, it has often been assumed that cell growth reflects the rate of accumulation of cellular macromolecules. Because protein and RNA, the most abundant macromolecular constituents of E. coli, increase approximately exponentially during the cell cycle (22), this assumption has led to the conclusion that individual cell growth is essentially exponential (9). However, the assumption is unwarranted because pool magnitude, although small, are not negligible and growth is strongly dependent on the variation in pool magnitude during the cell cycle, as shown below.The relationships among the average values for total, macromolecular, and pool dry weights are shown in Fig. i for three different growth models, exponential, linear, and * Corresponding author.bilinear. The macromolecular fraction was a...