The utilization of carbon from 14C-labeled glucose by adriamycin (ADM)-sensitive and -resistant LoVo human colon carcinoma cells has been investigated. The following summarizes the results: 1. Aerobic glycolysis is the main energy-yielding process in both cell lines, whereas only a small proportion of glucose carbon atoms are incorporated into CO2, lipids, nucleic acids, and supporting structures. 2. Basic alterations in glucose metabolism are associated with drug resistance in tumor cells. In fact, ADM-resistant LoVo cells show a significant increase in the oxidative pathway of glucose metabolism as well as in acetyl-CoA production. 3. In adriamycin-resistant LoVo cells, the amount of glucose carbon atoms metabolized through the pentose phosphate pathway is significantly higher than in adriamycin-sensitive cells. These findings confirm a modified glucose metabolism in cells with a resistant phenotype.