Objective. To investigate the effect of metronidazole (MT) on the antitumor activity and toxicity of 5-fluorouracil (5-FU). Material and methods. The antitumor effect of 5-FU and its combination with MT on the dynamics of growth of B16 melanoma and CaO-1 ovarian carcinoma was studied in vivo in С57Вl/6 and CBA/Lac mice, respectively. Results. 5-FU inhibited the growth of CaO-1 ovarian carcinoma and did not significantly affect that of B16 melanoma. The effect of the radiation sensitizer MT on the antitumor activity of the cytostatic drug depended on the time of MT administration. The use of MT two hours before 5-FU injection enhanced the antitumor effect of the latter in mice inoculated with CaO-1 carcinoma. When administered 12 hours before 5-FU injection, MT failed to affect the antitumor effect of the cytostatic drug. The combination of 5-FU and MT did not overcome B16 melanoma resistance to 5-FU. When used 4 hours prior to 5-FU injection, MT enhanced the toxicity of the cytostatic agent by 1.5—2 times. This enhanced toxicity resulted even in an increase in the animals’ deaths. Conclusion. In clinical practice the time interval between the use of MT and cytotoxic drugs should be at least 30 hours in terms of the ratio of elimination half-life of the drugs in mice and humans.