In a prospective phase I/II trial, EMD 55,900, a murine monoclonal antibody (MAb) directed against EGF receptor, was administered at tumour recurrence to 16 patients previously treated with surgery, radiotherapy and chemotherapy for high grade supratentorial gliomas (11 glioblastomas, five anaplastic astrocytomas). Duration of treatment was planned for at least 4 weeks. The first 10 patients received 40 mg of MAb three times per week (median cumulative dose, 760 mg) and the last 6 patients received 200 mg three times per week (median cumulative dose, 2400 mg). Serum levels of EMD 55,900 were proportional to the injected dose. Repeated infusions of EMD 55,900 were well tolerated. In 13/16 patients, there were no adverse events. Among the 3 others, one had a grade IV neutropenia, one had a clinically asymptomatic hepatitis, and one had a skin rash. This last patient was the only one who had increased human antimouse antibodies (HAMA). After 4 weeks of therapy, 13 patients were evaluable for response. No measurable tumour regression was obtained with either schedule. 6 of the 13 patients (46%) showed evidence of progressive disease, while 7/13 (54%) had stable disease. All patients had progressive disease by 3 months. In this study, repeated infusions of EMD 55,900 were well tolerated but no therapeutic benefit was demonstrated.