Myopathy may occur as a complication of human immunodeficiency virus type 1 (HIV) infection or from its treatment, zidovudine (ZDV). We reviewed our experience with HIV-infected subjects referred for neuromuscular evaluation and compared features of myopathy in ZDV-treated (+ZDV) and untreated (-ZDV) patients. Fifty patients had myopathy, 25 diagnosed by pathologic criteria and 25 by clinical and other laboratory support. Twenty patients with myopathy had weight loss sufficient for the diagnosis of HIV wasting syndrome. Thirty-one subjects were +ZDV and 19 were -ZDV. Patients in each group presented with proximal weakness, although myalgia was more common in +ZDV patients. Both groups had elevated serum CK to a similar degree (medians: +ZDV, 485; -ZDV, 471). Muscle biopsies revealed myofiber degeneration, variable inflammatory infiltrates, inclusion bodies, and mitochondrial abnormalities in both groups. We followed response to ZDV withdrawal in 15 patients. Four had increased strength, three noted less myalgia, and eight had no clinical improvement. Twelve of 13 patients improved with prednisone. Although it is difficult to distinguish the myopathies of HIV and ZDV by clinical or pathologic criteria, in the majority of our patients, myopathy is due to HIV rather than ZDV.