Previous research has documented significant acceleration of tumor growth in animals receiving short-term parenteral nutrition. This study was performed to determine the effect of long-term enteral protein intake on tumor cell cycle kinetics in the tumor-bearing host. Fifty Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive a standard protein diet (22.0% protein; 4.20 kcal/g) or protein-depleted diet (0.03% protein; 4.27 kcal/g). Animals were sacrificed after 7 or 14 days on each diet and tumor cytokinetics determined by flow cytometry. Tumor volume was significantly reduced in animals receiving the protein-depleted versus standard protein diet after 14 days (P < 0.01). No difference was found in tumor cell cycle kinetics (% G0/G1, S, or G2/M populations) or tumor growth fraction (S + G2/M) in animals receiving standard or protein-depleted diet after 7 or 14 days. These results suggest that reduced tumor growth with prolonged protein depletion in this model occurs by either (a) movement of tumor cells from the active cell cycle to the dormant G0 state or (b) uniform increase of cell cycle duration without changing the relative proportion of cells throughout the cell cycle. The potential therapeutic implications of nutrient-induced alterations in tumor growth are discussed.