Sixteen patients with advanced malignancy were treated with rDNA alpha-2b interferon using a continuous 6-week i.v. schedule. Patients received 1 microgram, 3 mu [corrected], 5 mu and 7 mu/m2/day via a portable infusion pump system, all therapy being on an outpatient basis. The dose-limiting toxicity occurring at 7 mu/m2/day [corrected] was lethargy and somnolence. Five million units (mu) was the maximum tolerated dose but significant nausea, anorexia and lethargy affected 4/5 patients at this level. A dose of 3 mu/m2/day was well tolerated, producing little disturbance of normal activity in the majority of patients. Suppression of WBC and platelets was seen at all doses but was not dose-limiting. There was increasing severity of derangement of hepatic transaminases with increasing dose, and the occurrence of liver toxicity appeared to correlate with nausea, anorexia and lethargy. Assay of serum interferon during the infusion showed that this system maintained a constant level of interferon in the blood. However, the increase did not show a linear pattern with increasing dose, suggesting saturation of metabolic inactivation at 7 mu/m2/day. We recommend that a dose of 3 mu/m2/day be used in future studies of prolonged infusions of alpha-2 interferon.