Seventeen cases of disseminated herpes simplex virus (HSV) infection have occurred during pregnancy. Acyclovir therapy was associated with prolongation of the time from admission until spontaneous rupture of the membranes or delivery and an improved maternal outcome. This life-threatening condition has a typical presentation, which includes a nonspecific viral prodrome. During pregnancy, fever and anicteric hepatitis unresponsive to empiric antibiotics should prompt an evaluation for disseminated herpes simplex. Pharyngitis or skin lesions with a positive herpes simplex culture are common, specific signs associated with dissemination. The fever resolves within 48 hours in response to acyclovir therapy. One case of maternal disseminated HSV occurred at 22 weeks' gestation and resolved with acyclovir therapy; a healthy neonate was delivered vaginally at term.