The leptomeningeal reaction and the cerebrospinal fluid reaction of the canine inflammatory response were investigated concurrently. One-half milliliter cerebrospinal fluid (CSF) was withdrawn from the cisterna magna of 17 anesthetized mongrel dogs and analyzed. Using this same spinal tap, control and experimental animals were injected with 0.5 ml sterile saline and 0.5 ml defibrinated chicken erythrocytes, respectively. A second spinal tap was performed 2 to 168 hr later. The CSF from the first spinal tap contained less than 1 WBC/mm3. The cell population was unchanged in the second spinal tap of control animals. In experimental animals, the WBC population increased more than 100-fold by 24 hr. Polymorphonuclear cells (PMNs) appeared in the CSF first, followed by lymphocytes and monocytes. Injected erythrocytes seemed trapped in the subarachnoid space (SAS), especially in the inner sheet of the arachnoid mater. The leptomeninges had a substantial increase in free cells without fibrosis. Pial and leptomeningeal cells of the arachnoid trabeculae appeared swollen. Two hours after injection, chicken erythrocytes were phagocytosed by pial cells, macrophages, and free cells adherent to the leptomeninges. The epiplexus cell populations for saline-control and erythrocyte-experimental animals were similar, suggesting that the choroid plexuses were not a gateway for PMN, lymphocyte, or monocyte infusion into the SAS.