In the present study we evaluated the antitumour effect of genistein alone, cyclophosphamide alone and as a combined therapy with both agents in mice transplanted with B16F-10 melanoma and Lewis lung cancer cells. The influence of the route of inoculation of the tumour cells on the antitumour and antimetastatic effects of these therapeutics was evaluated. The antitumour effect of genistein in mice with B16F-10 intradermically (i.d.) growing tumours and in mice with LL2 subcutaneous (s.c.) tumours was observed. In addition, its antimetastatic effect (reduction of lung colonies) in mice inoculated intravenously (i.v.) with B16F-10 and in mice with LL2 cells injected either intravenously or subcutaneously was observed. No life span prolongation of mice injected intraperitoneally (i.p.) with B16F-10 cells was observed, either after treatment with genistein alone or with cyclophosphamide alone. The synergistic effect of both agents in combined treatment, when the cells of B16F-10 melanoma were injected i.p., i.v. or i.d. and in a weaker manner when the cells of LL2 cancer were injected s.c., was observed. When LL2 cells were injected intravenously, no additive effect of genistein and CY could be detected. In conclusion, we have described the experimental mouse tumour models in which both the antitumour and antimetastatic effects of genistein alone, CY alone and those of combined therapy with genistein and cyclophosphamide were dependent on the implantation route of the tumour cells.