The purpose of the present study was to examine mechanisms of activity- dependent changes of cerebral blood flow (CBF) in rat cerebellar cortex by laserDoppler fLowmetry, using two synaptic inputs that excite different regions of the same target cell and with different synaptic strength. The apical part of Purkinje cells was activated by electrical stimulation of parallel fibers, whereas the cell soma and the proximal part of the dendritic tree were activated by climbing fibers using harmaline (40 mg/kg ip) or electrical stimulation of the inferior olive. Glass microelectrodes were used for recordings of field potentials and single-unit activity of Purkinje cells. CBF increases evoked by parallel fibers were most pronounced in the upper cortical layers. In contrast, climbing fiber stimulation increased CBF in the entire cortex. Inhibition of nitric oxide (NO) synthase activity by N(G)-nitro-L-arginine (L-NNA) or guanylate cyclase activity by 1H- [1,2,4(oxadiazolo)4,3-a]quinoxaline-1-one did not affect basal or harmaline- induced Purkinje cell activity but attenuated harmaline- and parallel fiber- evoked CBF increases by ~40-50%. Application of 8-(p- sulfophenyl)theophylline and adenosine deaminase reduced the harmaline- evoked CBF increase without any effect on the parallel fiber-evoked CBF response. The results suggest that CBF increases elicited by activation of Purkinje cells are partially mediated by the NO-guanosine 3',5'-cyclic monophosphate system independent of the input function but that adenosine contributes as well when climbing fibers are activated. This is the first demonstration of variations of coupling as a function of postsynaptic activity in the same cell.