The Lewis lung carcinoma implanted subcutaneously in the hind leg of a C57BL mouse metastasizes avidly to the lungs of the host. This tumour model system thus allows assessment of both primary and metastatic disease to treatment. Lonidamine (50 mg/kg) administered once or twice daily produced approximately additive tumour growth delay with whole-body hyperthermia (60 min to 42 degrees C and 60 min at 42 degrees C). The addition of lonidamine to treatment with cisplatin (10 mg/kg) and whole-body hyperthermia continued to produce increased tumour growth delay of up to 14.7 days compared with 10.8 days for cisplatin/whole-body hyperthermia. The response of the metastatic disease paralleled that of the primary tumour with a reduction in the number and percent of large metastases (> 3 mm) on day 20 post-tumour implantation. The addition of local fractionated radiation therapy (3 Gy x 5) to the primary tumour produced a very effective treatment regimen resulting in 37.5 days of tumour growth delay along with twice daily lonidamine/cisplatin whole-body hyperthermia. With this treatment regimen there was also a reduction to 50% of control of the number of lung metastases as well as the percent of large metastases on day 20. Further investigation of these treatment combinations is warranted.