Myopathy and hepatic toxicity are important complications of zidovudine (3'-azido-3'-deoxythymidine therapy) in patients infected with the human immunodeficiency virus (HIV) both may also occur in HIV infection in the absence of zidovudine therapy. We report 2 cases of myopathy caused by zidovudine, occurring within 16 wks of initiation of therapy, and a case of concurrent hepatic and muscle toxicity. In one case, electron microscopy demonstrated characteristic enlarged mitochondria with paracrystalline inclusions. This technique can distinguish the myopathies caused by either HIV or zidovudine. Both zidovudine-induced myopathy and hepatoxicity require discontinuation of the drug if severe.