A 60 year old white man in previous good health presented with a 6 month history of progressive muscle weakness. Clinical and laboratory findings were typical of dermatomyositis. Muscle biopsy confirmed the presence of inflammatory myopathy; deposits of immunoglobulin G (IgG), immunoglobulin M (IgM) or third component of complement (C3) were not detected by immunofluorescence. No evidence was found for an associated neoplasm. An unexpected finding was the total absence of serum hemolytic complement activity. Further investigation revealed that the complement defect was attributable to a selective and total absence of the second component of complement (C2), as determined by both functional and immunoprecipitin assays. Family studies indicated that the defect was inherited in an autosomal recessive manner, as has been observed in the previously reported C2-deficient kindreds. This case demonstrates that typical muscle lesions of dermatomyositis can occur in the presence of a complement defect which would preclude activation of the classic (C1-C4-C2) complement pathway. The case is of further interest as one of a series of recently reported associations of rheumatic diseases with hereditary complement deficiencies. Study of the functional properties of the propositus' C2-deficient serum demonstrated normal generation of chemotactic activity in the presence of endotoxin or aggregated IgG, and normal or near normal bactericidal activity against Salmonella typhi O 901 and Hemophilus influenzae, type b. These findings emphasize the importance of the alternate (properdin) pathway of complement activiation in these functions.