We report that experimental glioblastoma grow more vigorously in A(1) adenosine receptor (A(1)AR)-deficient mice associated with a strong accumulation of microglial cells at and around the tumors. A(1)ARs were prominently expressed in microglia associated with tumor cells as revealed with immunocytochemistry but low in microglia in the unaffected brain tissue. The A(1)AR could also be detected on microglia from human glioblastoma resections. To study functional interactions between tumor and host cells, we studied glioblastoma growth in organotypical brain slice cultures. A(1)AR agonists suppressed tumor growth. When, however, microglial cells were depleted from the slices, the agonists even stimulated tumor growth. Thus, adenosine attenuates glioblastoma growth acting via A(1)AR in microglia.