Fatty acid-binding protein is considered to play an important role in fatty acid oxidation. Since diabetes mellitus causes marked changes of this latter metabolic process, we compared the effect of this pathological condition on both parameters in a comparative investigation of different rat tissues. Palmitate oxidation capacity and content of fatty acid-binding protein were determined in liver, heart and quadriceps muscle from rats with 2-week streptozotocin-induced diabetes mellitus and controls. In liver homogenates fatty acid oxidation capacity increased by 90%, but their content of fatty acid-binding protein decreased by 35%. Fatty acid oxidation capacity of heart and quadriceps muscle and fatty acid-binding protein content of quadriceps muscle did not change, but fatty acid-binding protein content of heart muscle doubled. Long-term diabetes (8 months) had a similar effect on content of this protein. In summary, changes of fatty acid oxidation capacity do not appear to correlate with fatty acid-binding protein content during the development of diabetes. This does not preclude other functions of fatty acid-binding proteins in regulation of lipid metabolism and processes in which fatty acids play a modulatory role.