To evaluate the efficacy of subconjunctival interferon-alpha for the treatment of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Small, noncomparative, interventional case series. Five patients with histologically proven conjunctival MALT lymphoma were studied prospectively. Patients were given 1,500,000 international units (IU) of interferon-alpha (IFN-alpha) (Roferon-A) subconjunctivally inside the lesion, three times a week for four weeks. If there was even a minimal response, a further cycle of 1,000,000 IU three times a week for four weeks was administered. Patients received a maintenance dose of 1 million IU, every 15 days for 4 times, after clinical resolution of the lesion. Patients were followed clinically, with slit lamp examination, for evidence of tumor disappearance or recurrence. Complete response was obtained in all patients. The lesion resolved completely by the eighth week. Four patients did not show any local recurrence with a median follow-up of 21 months (12-36 months). One patient presented with a recurrence after 11 months, in association with systemic lymphoma progression. Local chemotherapy with IFN-alpha seems to be an effective treatment modality, alternative to radiotherapy, for conjunctival MALT lymphomas.