Malignant pleural effusion is a common and significant source of morbidity for many patients with cancer. In an attempt to control this condition without using chest tube drainage, we administered recombinant interferon alpha-2b (INTRON, Schering-Plough, Kenilworth, NJ) intrapleurally via catheter after routine thoracentesis. Twenty-two installations of interferon were administered to 15 patients in incremental dosages of 3-50 x 10(6) U/m2. Of 20 evaluable treatments, six (30%) achieved effusion stabilization; there were no complete or partial responses. Only one of nine treatments at a dosage less than 20 x 10(6) units/m2 resulted in symptoms, while four of 11 treatments at the higher dosage were associated with transient fever, chills, and chest pain. Interferon demonstrated no major activity in this heavily treated patient population with advanced malignancy.