The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.