The effects of nitric oxide synthase (NOS) blockade on the cerebrocortical microcirculation were investigated under physiological conditions in anesthetized ventilated rats using laser–Doppler (LD) flowmetry. LD flow values of the parietal cortex were determined before and after systemic administration of the NOS inhibitor N^G-nitro-l-arginine-methyl-esther. NOS blockade reduced the LD flow significantly and the magnitude of the reduction was in close correlation with the baseline value. Synchronized sinus-wave-like LD flow oscillations were observed frequently after NOS inhibition and their appearance was also dependent on the high baseline flow values. These results indicate marked, baseline-dependent differences in the cerebrocortical blood flow response to the inhibition of the nitric oxide pathway, and may suggest that areas with high resting red blood cell flow express high NOS activity.