To evaluate the trade-off of toxicity versus improved clinical outcome with interferon alfa-2b (IFN) administered concomitantly with a doxorubicin-containing regimen for the treatment of advanced follicular lymphoma. A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms or Toxicity [Q-TWiST]) was applied to the Groupe d'Etude des Lymphomes Folliculaires (GELF) trial 86, which compared a regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) versus CHVP plus IFN in 242 patients with confirmed follicular lymphoma. CHVP was administered monthly for 6 months then every other month for 12 months. The IFN dosage was 5 x 10(6) U three times weekly for 18 months. After a median follow-up duration of 72 months, the IFN group gained a mean of 12.3 months of progression-free survival (PFS) and 7.4 months of overall survival (OS), but also experienced additional time with grade 3 or worse toxicity compared with the CHVP group. Sensitivity analysis demonstrated that CHVP plus IFN provided a greater amount of quality-adjusted survival regardless of the relative quality-of-life valuations placed on time with toxicity due to CVHP alone, time with toxicity due to CHVP plus IFN, and time following disease progression. This gain was significant (P < .05) in all cases except for patients who consider time with toxicity to have a low relative value and time following disease progression to have a high relative value. In patients with advanced follicular lymphoma, the clinical benefits of concomitant IFN can significantly offset the associated grade 3 or worse toxic effects. The magnitude of this clinical benefit depends on an individual patient's relative quality-of-life valuations for time with toxicity and time following disease progression.