Fifteen patients with progressing melanomas, hypernephromas or B-cell malignancies were treated in a phase I study with Interferon (IFN) alρha-2a by continuous subcutaneous infusion. With the help of a syringe driver pump daily doses of 12–15 MU resulting in median weekly doses of 90 MU could be safely given with little side effects. Flu-like symptoms and side effects from the gastrointestinal tract were mainly of grade 1 or 2 only. The major dose limiting but reversible toxicity was leukopenia. Five patients developed local inflammatory reactions at the infusion site. The pharmacokinetic data demonstrate that by this route of administration median serum levels of 54 IU/ml (range 9.6–192.0 IU/ml) (EIA-F-assay) can be achieved. Antibody formation was observed in 4 patients. – One out of 9 patients evalu-able for tumor response demonstrated a partial tumor regression and 4 patients had a stabilisation of their disease. In comparison to intermittent i.m. or s.c. schedules, this novel route of administration by continuous subcutaneous infusion results in significant serum concentrations, biological activity and little clinical side effects. This may facilitate in the future the combination of IFN alpha-2a with other biological response modifiers like interleukin-2 or tumor necrosis