In the present study, the vasomotor effects of nicotine, its interaction with local chemical factors and norepinephrine, and its effects on the permeability of the blood-brain barrier (BBB) were investigated. Using perivascular microapplication, 10-6 M nicotine was found not to exert a vasomotor effect by itself or to modify the vasodilating effect of an increase in perivascular H +, K + and adenosine concentration. The constrictor effect of a decrease in H +, K + or an increase in norepinephrine concentration in the perivascular space was also not altered by 10-6 M nicotine, indicating a lack of interaction between nicotine and the compounds tested. Using cortical superfusion and intravital fluorescence microscopy nicotine (10 -7 to 10 .3 M) was also found not to affect the diameter of pial arteries during superfusion periods of 30 rain each. The integrity of BBB could be demonstrated in time-matched solvent controls over 3 h using intravenously-infused FITC-labelled dextran (MW 70 000) as tracer. During cortical superfusion with 10 -7 to 10 .5 M nicotine the permeability of the BBB was not increased compared with the time-matched controls. However, during superfusion with 10-4 and 10-3 M nicotine, tracer extravasation could be quantified by computer-aided image analysis. The extravasation index (EI) increased by up to eight times. These data indicate that only toxic concentrations of nicotine increase BBB permeability to FITC-dextran 70000.