To address the role of nerve growth factor (NGF) in diabetes mellitus (DM)-induced cardiac autonomic neuropathy, we quantitated and compared the expression of NGF mRNA in the cardiac and the skeletal muscle in experimental DM mice with the RT-PCR-HPLC method, which we have developed previously, using a NGF deletion mutant RNA as an internal standard. DM was induced in ICR mice via intraperitoneal injection of streptozotocin. RT-PCR was performed using total RNA extracted from left ventricle and soleus muscle, and the levels of NGF mRNA were quantitated by HPLC analysis. NGF mRNA content of the cardiac muscle was 17-fold higher than the skeletal muscles in control mice. NGF mRNA content of the cardiac muscle in diabetic mice at 6 weeks was 4.0-fold higher than that in the control mice, while that of the skeletal muscle in diabetic mice was not different from the controls. These results indicated that the DM-induced increase in NGF mRNA content was higher in cardiac muscle than skeletal muscle, and that NGF might play an important role in cardiac autonomic neuropathy.