Canine cyclic hematopoiesis (CH) was first described in Gray Collies as the lethal gray syndrome, and was subsequently shown to be a counterpart of human cyclic neutropenia (CN). The disease is characterized by a recurrent cyclic change in the levels of neutrophils and other blood elements at approximately 12-day intervals. It is caused by an autosomally recessive gene with pleiotropic effects or a CH gene which is closely linked to a gray color gene. The infectious insult on affected animals is periodic but its clinical and pathologic effects are continual and cumulative Affected dogs die after weaning and rarely survive over 6 months of age. There is evidence of immunoregulatory defects in these dogs. Reciprocal bone marrow transplantation indicates that the defect resides in the bone marrow, but the actual site and mechanism of the defect has not been established. The disease in Gray Collies represents a unique model system for studying the mechanism of cyclic hematopoiesis and hematopoietic regulation. Studies of the disease have made conceptual contributions toward understanding and treatment of human cyclic neutropenia.