In primary cultures of cerebellar granule cells, the gamma aminobutyric acid B (GABAB) receptor couples to an inhibitory mechanism of adenylate cyclase. The inhibition of adenylate cyclase can be observed either by the measurement of cellular cyclic AMP content or by in vitro measurement of adenylate cyclase from plasma membrane of these cerebellar granule cells. The GABAB receptors can be stimulated by GABA and the GABA analog, baclofen. This receptor-mediated inhibition of adenylate cyclase was blocked by the pertussis toxin, islet-activating protein. Furthermore, the authors show that islet-activating protein catalyzed the ADP ribosylation of the guanine nucleotide inhibitory unit (MW 41,000) in the cerebellar granule cells. In summary, the authors provide evidence supporting the presence of a GABAB receptor in the cerebellar granule cells and suggest that this receptor couples with the guanine nucleotide inhibitory unit to inhibit the formation of cyclic AMP.