The effect of cardiomyopathy development on the biosynthesis of polyglycerophospholipids in the hearts of UM.X-7.1 cardiomyopathic Syrian hamsters (strain CHF.146) was investigated. Phosphatidylglycerol and cardiolipin content (expressed per freeze-dried ventricular weight) was reduced progressively in cardiomyopathic hamsters from 60 to 200 days. However, the reduction was developmental and was not specific to the disease state since age-matched controls (strain CHF.148) exhibited a similar reduction in these phospholipids. In addition, there was no decrease in the pool size of these and all other phospholipids during development when expressed as a percent of total phospholipid phosphorus. Hearts from 60 and 200 day old control and cardiomyopathic hamsters were perfused with [1,3-³H]glycerol for 60 min and the radioactivity incorporated into phospholipids determined. Radioactivity incorporated into all phospholipids were unaltered between 60 and 200 day old hamsters indicating that the rate of de novo phospholipid biosynthesis from glycerol was not affected by development of the disease. Phospholipid content was then examined in the hearts of 200 day  old  cardiomyopathic  Syrian hamsters  treated for 3 days with streptozotocin. Cardiac phosphatidylglycerol content, but not that of other phospholipids, was reduced 30% (p<0.05) in diabetic and 60% (p<0.05) in diabetic cardiomyopathic hamsters compared with untreated controls. Thus, diabetes superimposed on cardiomyopathy resulted in a further reduction  in phosphatidylglycerol content than the diabetic  state alone. Hence, the Syrian hamster appears to be a new and useful model to study regulation of phosphatidyglycerol metabolism in diabetic cardiomyopathy.