Chemoimmunotherapy of pulmonary metastases was investigated in a protocol of combined anti-tumour agents and interferon-β and/or interleukin-2. The combination of interferon-β and interleukin-2 after treatment with etoposide or cisplatin exerted profound therapeutic effects in an experimental model (lung colonization) using colon carcinoma 26, which was resistant to interferon-β or to interleukin-2 alone. Cured mice treated with anti-tumour agents and cytokines rejected re-implanted tumours. Moreover, this approach also had profound effects on spontaneous pulmonary metastases, together with the effect on primary tumours. However, this combination of cytokines did not enhance the anti-tumour activity of etoposide in athymic mice with pulmonary metastases. Injections of tumour-bearing BALB/c mice with a combination of etoposide and these cytokines resulted in a marked increase in CD8 ⁺,asialo-GM1 ⁺ cells. Thus the combined treatment with interferon-β and interleukin-2 after administration of cytotoxic drugs may induce specific anti-tumour immunity, and such combinations may offer a new approach to the development of effective therapy for cancer metastases.