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To confirm the positive results of a preliminary trial, 26 patients with mixed cryoglobulinaemia were enrolled in a controlled, randomised, crossover trial with interferon alfa-2b. A significant improvement was seen in the purpura score and alanine aminotransferase activities during six months' treatment, and was associated with a significant decrease in cryocrit and a returning to normal of the lymphocyte CD4/CD8 ratio (in eight of nine patients). No significant variations were seen during the six month period without interferon. Only six patients withdrew from treatment, three because of side effects and three because of poor compliance.