A most unusual inflammatory myopathy, called macrophagic myofasciitis, first described by the Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD), a specific branch of the Association Française contre les Myopathies was recorded with an increasing frequency from 1993 in the main French myopathologic centers. In October 1999, 65 macrophagic myofasciitis cases were recorded since our first description. We described the characteristics of the first 22 patients. The 22 patients (sex-ratio M/F, 1:3) were referred with the presumptive diagnosis of polymyositis (11), polymyalgia rheumatica (five), mitochondrial cytopathy (four), and congenital myopathy or muscle dystrophy (one each). Symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). Abnormal laboratory findings included elevated CK levels (50%), markedly increased ESR (37%), and myopathic EMG (35%). Muscle biopsy showed a unique myopathologic pattern characterized by 1) centripetal infiltration of epimysium, perimysium, and perifascicular endomysium by sheets of large cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-), with a PAS-positive content; 2) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; 3) presence of occasional CD8+ T-cells; 3) inconspicuous muscle fibre damage. The picture was easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. The infectious diseases could not be documented in our patients. Patients improved under steroid therapy, associated or not with nonspecific antibiotic therapy. The authors discuss the main etiologic hypothesis of the macrophagic myofasciitis.