A pharmacokinetic study was performed with partially pure immune (gamma) interferon (IFN-gamma) in patients with metastatic cancer. Nine patients were given IFN-gamma by the i.m. route in doses ranging from 1.5 X 10(5) to 9.6 X 10(6) antiviral units. There was no detectable antiviral activity in patients' serum, and only minimal side effects were observed. Fifteen patients were given IFN-gamma by i.v. bolus infusion in doses ranging from 1.5 X 10(5) to 54 X 10(6) units. Serum clearance of antiviral activity was described by a monoexponential disappearance curve. The serum half-life was dose dependent (3 min at the lower doses and 34 min at the highest doses). There were few consistent biological effects observed in the patients. Based on these pharmacokinetic data, eight patients were treated by a 6-hr continuous infusion consisting of 3 X 10(6) units by i.v. bolus followed by 4 X 10(6) units/hr for 6 hr. This regimen resulted in consistent serum levels of IFN-gamma ranging from 40 to 60 units over the 6-hr period. Marked granulocytopenia occurred within 24 hr and was sustained during the 10-day infusion period. There was marked increase in serum beta 2-microglobulin. We conclude that, in order to induce consistent serum antiviral activity, partially pure IFN-gamma, because of its rapid serum disappearance curve, must be administered by continuous i.v. infusion.