A previously healthy 25-year-old man developed a spontaneous rupture of the spleen during a cytomegalovirus (CMV) infection. The only other clinical feature was a well tolerated fever of 37.5 degrees C to 39 degrees C during the month before. The diagnosis was confirmed by the presence of IgM antibodies to CMV in the serum and by typical intranuclear inclusions for CMV identified by splenic histopathological findings. The patient recovered completely. Spontaneous splenic rupture is uncommon in primary cytomegalovirus infection.