The effects of nicotine and electric foot shock as well as of their combination on blood serotonergic measures and on whole blood aggregation have been analyzed. In rats subjected to electric footshock a rise (p < 0.05) in plasma but not in whole blood serotonin was observed, whereas this parameter was not influenced in nicotine-treated rats when compared to the control group. The combination of nicotine with electric footshock only slightly increased plasma serotonin and showed no effect on whole blood serotonin, but 5-hydroxyindole acetic acid (5-HIAA), the major metabolite of serotonin (5-HT), as well as the 5-HIAA/5-HT ratio were markedly increased (p < 0.01) suggesting an enhanced turnover of 5-HT under these conditions. The collagen-induced aggregation in whole blood was not influenced in nicotine-, in footshock- nor in combined-treated rats when compared to the controls. Our data indicate that stress as well as the combination of stress with nicotine may affect the serotonergic system which is in contrast to the exposure to nicotine alone.