Graded levels of high-molecular-weight carrageenan were fed to male Fischer 344 rats to investigate the effects of carrageenan on colonic cell proliferation. Four groups of 7 rats consumed diets containing 0 (control), 0.65, 1.31, or 2.61% carrageenan ad libitum for 4 wk. These levels were designed to simulate (on a milligram-per-kilogram basis) 25, 50, and 100 times the maximal human carrageenan intake. After an overnight fast, the rats were anesthetized, and the colonic mucosa was removed and homogenized. A supernatant was prepared and assayed for total protein and thymidine kinase activity (a marker for cell proliferation). Increasing levels of carrageenan resulted in stepwise increases in total mucosal protein and in thymidine kinase specific (units per milligram of protein) and total (units per centimeter of colon) activity. However, increases in thymidine kinase activity were statistically significant only at the highest dose of carrageenan. No histological abnormalities were associated with any level of carrageenan feeding. These results suggest a clear dose-response increase in colonic mucosal cell proliferation with increasing doses of carrageenan; however, the effect at doses approximating 19 times maximal human intake was not statistically different from that for control rats under the conditions of this study.