Two patients with advanced Wegener's granulomatosis, one with nose, sinus, and skin involvement and the other with pulmonary, renal, and skin involvement, experienced marked improvement with intermittent methotrexate therapy. Initial treatment consisted of weekly intravenous injections of 50 mg. This was subsequently decreased to 15 and 25 mg as a single, weekly oral dose. Responses consisted of marked and rapid subjective relief of symptoms, healing of skin lesions, total clearing of pulmonary infiltrates, and lack of progression of nasal, sinus, and renal lesions. Remission of the disease, for more than 30 and 26 months, respectively, has occurred without evidence of oral or hematologic toxicity of methotrexate.