We followed the concept that the chemical reactivity of ozone depends upon its oxidative properties. Activated oxygen species are causally involved in toxicity of certain chemotherapeutic drugs. We have tested this prediction in human cell cultures either to overcome chemoresistance and/or to increase chemical cytotoxicity. Our results indicate that ozone in combination with 5-fluorouracil (5-FU) makes a 5-FU-resistant cell line susceptible for the combined treatment modality. Furthermore, ozone acts synergistically or at least additive to chemotherapy in different tumor cell suspensions, derived from the breast and the colon.