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Aim. To investigate the influence of titanium dioxide nanoparticles (TiO2) on histamine-, nicotine- (acetylcholine- nicotine)-stimulated modulations of mechanical activity in smooth muscles of caecum and stomach of rats. Methods. Electronic scanning microscopy; zeta-potential estimation; the isometric tension recordings; pharmacological and kinetic analysis. Results. Relaxation of smooth muscles stripes (SMS) of caecum stimulated by 10-5 mol/l nicotine on the background of histamine contraction was not affected by TiO2 (10-3 mg/ml); under the same conditions TiO2 reinforced the histamine-induced contractions. The cumulative increase in TiO2 concentration in the 10-6-10-4 mg/ml range was accompanied by inhibition of SMS contractions stimulated by histamine (10-5 mol/l) and nicotine (10-7 mol/l). Similar results were obtained on stomach SMS. The phase component of acetylcholine contraction modulated by nicotine was bound to be unaffected by TiO2 whereas the tonic component was inhibited. Conclusions. The suspension of TiO2 nanoparticles in conditions of cumulative effect modulates the mechanisms of neurotransmitter release from neurons of intramural plexuses of circular smooth muscle of the gastrointestinal tract which are activated by histamine and nicotine (10-7 mol/l). [ABSTRACT FROM AUTHOR]