We here describe an unusual case of multifocal eosinophilic granuloma ("Hand-Schuller-Christian disease") in a middle-aged woman. The case underscores the varied and subtle nature of the disease presentation and the extent to which many organ systems may become involved. Unusual features of her case include atypical bone roentgenograms, cutaneous anergy, panhypopituitarism and evidence of diffuse central nervous system dysfunction. Several features of multifocal eosinophilic granuloma present in the older age group are different from those presenting in children and young adults. Finally, multifocal eosinophilic granuloma may present all the cllinical and laboratory features of a progressive, chronic disease.