Previous reports have suggested that HIV-related wasting syndrome may be considered as a form of myopathy. The aim of the present study was to investigate histopathological muscle changes in HIV-related wasting syndrome in order to know if there is a common substrate and whether muscle plays a primary or secondary role in its development. Patients with wasting syndrome diagnosed by Centers for Disease Control (CDC) criteria were prospectively evaluated. Clinical, analytical, nutritional, anthropometrical and muscular data were recorded. The patients were subdivided into two groups: group A was constituted by patients in whom wasting syndrome was the AIDS-defining illness, and group B by patients in whom AIDS diagnosis was previously made. In all cases muscle biopsy was performed and processed for conventional stainings and histochemical reactions. Thirty patients were included (group A, 12; group B, 18). Clinical, analytical, nutritional and anthropometrical data did not essentially differ between the two groups. All patients were malnourished with respect to controls. Histopathological findings in muscle biopsy were heterogeneous and similar in both groups, except for HIV-related myopathies, which were more frequently seen in the patients from group A (P=0.05). In five cases (17%) an unsuspected and potentially treatable myopathy was diagnosed. Patients with polyarteritis nodosa (two) or polymyositis (one) were treated with prednisone, which improved their wasting syndrome. By contrast, patients with AZT-myopathy (two) did not improve when the drug was discontinued. We conclude that in most cases the wasting syndrome cannot be considered as a true myopathy, and probably metabolic and/or nutritional factors may account for wasting development. However, in a subset of patients muscle biopsy allows the diagnosis of a treatable myopathy leading to the improvement of wasting syndrome.