Neurological side effects and complications of cryoglobulinemia were observed during interferon-alpha (IFN-alpha) therapy in a patient with chronic myeloid leukemia (CML). A 50-year-old man was hospitalized because of leukocytosis and extramedullary tumors in the lumbar spine. In addition, the patient complained of dysesthesia in his feet. A diagnosis of accelerated phase CML was made. Administration of prednisolone, vincristine, hydroxyurea, and Ara-C and irradiation of the lumbar spine were started. Two months later, the patients achieved hematologic response and the size of his tumors decreased. Thereafter, we started IFN-alpha treatment (3-6 x 10(6) units daily) by intramuscular injection. After 8 weeks of this treatment, the patient complained of worsening dysesthesia in his feet. An axonal form of peripheral neuropathy was diagnosed by electrophysiological examination. Immunological studies revealed decreased complement levels and type III mixed cryoglobulinemia. Methylprednisolone pulse therapy alleviated the neurological symptoms and lowered the cryoglobulin levels. The clinical course suggested that mixed cryoglobulinemia was associated with CML and that the increase in cryoglobulin levels was caused by IFN-alpha and played a causative role in the worsening peripheral neuropathy. Therefore, to prevent these side effects, careful clinical assessment is necessary before starting IFN-alpha therapy.