Cachexia is a common syndrome seen in patients suffering from sepsis, AIDS and cancer and is characterized by severe muscle wasting. Although the decline in muscle mass associated with the presence of a tumor has been well described there is little known about the effect of cancer cachexia on the relative expression of contractile protein isoforms such as myosin. Other interventions that induce muscle atrophy are known to cause a shift in expression of myosin isoforms, such that the faster (type II) forms of myosin are increased. We injected mice with murine C-26 adenocarcinoma cells, a tumor cell line that has previously been shown to be associated with significant muscle wasting. These mice, as well as age-matched controls, were sacrificed 21 days following tumor injection and the soleus, plantaris and gastrocnemius muscles were excised and weighed. The muscles were homogenized and total protein concentration was determined. Myosin heavy chain (MyHC) and myosin light chain (MLC) content was determined by SDS-PAGE. We found that body weight was significantly lower in tumor bearing mice (T) compared to control (C). There was a significant decrease in muscle mass in all three muscles tested compared to control with the largest decrease occurring in the soleus muscle. We found that while no type IIb MyHC was detected in the soleus samples from C mice, in the soleus muscles from T mice type IIb MyHC comprised 19% of the total MyHC. This increase in type IIb MyHC was accompanied by a concomitant decrease in type I MHC content (33% in T vs. 52% in C). MyHC isoform content in plantaris and gastrocnemius from T mice were not significantly different from control. Fast isoforms of MLC1 and MLC2 were also increased in the tumor bearing soleus. These data are the first to show a change in myosin isoform expression accompanying the muscle atrophy during cancer cachexia.