A patient with disseminated herpes simplex virus infection, documented by direct immunofluorescence, and untreated multiple myeloma with abnormal immunoglobulins is presented. Reports of infections with intracellular pathogens in myeloma patients are rare, whereas pyogenic infections have been amply documented. Partly in consequence of this, the untreated disease has been thought of as a relatively pure defect in humoral immunity. Review of present knowledge suggests that cell-mediated immunity is of paramount importance in combatting and containing infection with this virus. Thus, immune defects in multiple myeloma, and its infectious complications, may be more complex than appreciated by current concepts of this disease based on previously reported cases.