The rate of protein synthesis in vivo was assessed in tumor tissue, skeletal muscle, liver, and the whole body of rats bearing either the Yoshida sarcoma or Novikoff hepatoma after 18 days of tumor growth and compared to tumor-free controls. Changes in size of the whole animal and tumor (i.e., growth) were measured, and fractional rates of growth, synthesis, and degradation were estimated. Muscle protein synthesis and whole-body growth were significantly reduced in both groups of tumor-bearing rats after 18 days of tumor growth. In addition to reductions in muscle protein synthesis, whole-body protein synthesis was significantly reduced in the Yoshida tumor-bearing group (587 +/- 36 versus 401 +/- 40 mg/h; mean +/- SEM; control versus Yoshida group, respectively, P less than 0.01). Tumor protein synthesis was not statistically different between the Yoshida tumor (76 +/- 21 mg/h) and the Novikoff tumor (50 +/- 8) after 18 days of growth despite the fact that the Yoshida tumors were significantly larger (33.9 +/- 4.2 g versus 11.9 +/- 1.2 g; P less than 0.01). The fractional synthesis rate (Ks) was, in fact, significantly slower in the Yoshida versus the Novikoff tumor (36.8 +/- 7.6 versus 55.1 +/- 4.8%/day). Tumor growth (Kg) followed first order growth rates for both tumor types (r = 0.945, 0.869; Kg = 17.2 +/- 1.6, 15.5 +/- 1.9%/day; Yoshida and Novikoff, respectively). The fractional degradation rate of tumor protein (Kd) was determined as the difference between the two first order rate constants Ks and Kg. The tumor protein degradation rate was significantly reduced in the Yoshida tumors compared to the Novikoff tumors (19.6 +/- 8.2% versus 39.6 +/- 4.2%/day, respectively). The greater size in the Yoshida sarcoma can be attributed to reduction in fractional protein degradation rather than change in synthesis rates, which supports the theory that some tumors can regulate their growth by alteration in tumor protein degradation rates (J. A. Tayek et al., Cancer Res., 46:5649-5654, 1986).