In the present study, the interaction of inhalational and oral exposure to manganese and lead was investigated. Young adult male Wistar rats (2 x 10 per group) were treated orally with MnCl2 (15 and 60 mg/kg b.w.) or Pb acetate (80 and 320 mg/kg) for 3 or 6 weeks. Then, one half of the groups was further treated by intratracheal instillation of nanoparticulate MnO2 (2.63 mg/kg) or PbO (2 mg/kg) for an equal period of time. Body weight gain and signs of general toxicity were regularly checked. Finally, the rats’ motor behavior was tested in an open field box, and their spontaneous and evoked cortical electrical activity was recorded in urethane anesthesia. MnO2 nanoparticles caused disproportionately strong reduction of body weight gain but with Pb the weight effect was more dependent on dose. In the open field test, Mn caused hypomotility, more strongly after 6 weeks oral plus 6 weeks intratracheal than after 6 weeks oral treatment. Pb-treated rats showed increased ambulation but less rearing and somewhat longer local activity. Spontaneous cortical activity was shifted to higher frequencies after oral Mn application, but this change was not intensified by subsequent nanoparticle application. Oral Pb had an opposite effect. Cortical evoked potentials showed latency lengthening. In several cases, the effect of Mn and Pb was about as strong after 3 weeks oral plus 3 weeks intratracheal as after 6 weeks oral administration, although the summed dose was ca. two times lower in the former case. There can be a more-than-additive interaction between the amounts of heavy metals entering the organism in different routes and chemical forms.