Fifteen consenting patients with brain metastases recurrent after cranial irradiation were treated with intraarterial mitomycin-C, 15 mg/m2, administered in a total final volume of 100 ml 0.45% saline over 20 min through a transfemoral catheter with a 0.2-mu in-line filter. There were 2 early deaths (one probably drug-related). Of the 13 evaluable patients, 6 (46%) responded, with both computed tomography (CT) scan and neurological improvement. Median response duration was 25 weeks, and median survival of all 15 patients was 17 weeks. Neurological, ocular, and local skin toxicity were dose-limiting. The degree of toxicity was comparable to that we have noted with other intracarotid regimens, and it appears to be less toxic when infused into the vertebral artery than are most other drugs (although experience is still limited and caution still needs to be exercised). We do not recommend that this replace or be added to cranial irradiation as front-line treatment of brain metastases, but we feel that it is an effective and reasonably well-tolerated regimen for treatment of brain metastases that have recurred after cranial irradiation. We are currently initiating studies of intraarterial mitomycin-C combined with intraarterial cisplatin and teniposide (VM-26) as treatment for recurrent brain metastases.