Comparison of rituximab versus Iodine I 131 Tositumomab therapeutic regimen in subjects with follicular non Hodgkins B cell lymphoma. 506 subjects will be enrolled at 30 to 40 sites in the US, Canada, and Europe. Subjects will be randomly assigned to one of two treatment arms. In Arm A, subjects will receive 375 milligrams/meter2 (mg/m2 )of rituximab, given as an intravenous (IV) infusion once weekly for 4 weeks. In Arm B, subjects will undergo a two-phase treatment. In the first phase, termed the "dosimetric dose," subjects will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of 5 millicuries (mCi) (0.18 gigabecquerel [GBq]) of Iodine 131 Tositumomab (35 mg). Whole body gamma camera scans will be obtained three times (Day 0; Day 2, 3, or 4; and Day 6 or 7) following the dosimetric dose. The information derived from the scans will enable a patient specific dose to be calculated to deliver the desired total body dose of radiation (65 or 75 centigray [cGy]). In the second phase, termed the "therapeutic dose," subjects in Arm B will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of the subject specific activity of Iodine 131-conjugated Tositumomab (35 mg). Thyroid blockade will be implemented 24 hours prior to the dosimetric dose and continued for 14 days following the therapeutic dose. Subjects on study will be followed for response and safety at Week 7, Week 13, and every three months for the first and second year, every six months for the third year, and then annually for the forth and fifth years; and then for vital status, additional therapy, and long term safety events through year ten. Follow Up after subsequent NHL therapy will be carried out to assess tolerance of next anti-lymphoma therapy, development of myelodysplasia (MDS)/acute myelogenous leukemia (AML), HAMA or hypothyroidism, unexpected safety issues, and death.

• Drug: Iodine I 131 Tositumomab Therapeutic Regimen
• Drug: Rituximab

Inclusion criteria:

• Histologically confirmed diagnosis of follicular lymphoma
• Recurrent lymphoma after one or two qualifying therapy regimen(s)
• Patients must not have progressed within 4 weeks of their last chemotherapy dose
• Rituximab may have been used once as a single agent, in one continuous course of 4-8 weekly infusions (10-week period), or in combination with chemotherapy in a single prior treatment
• Patients whose prior therapy includes rituximab must have had a 6 month or greater response duration following the rituximab-containing regimen.
• Performance status of at least 70% on the Karnofsky Scale and an anticipated survival of at least three months
• Adequate absolute neutrophil count and platelet count within 21 days of study entry without support of blood products/growth factors
• Adequate renal function and adequate hepatic within 21 days of study entry
• Measurable disease, with at least one lesion measuring >/=2.0 cm x 2.0 cm by CT scan
• Human Anti Mouse Antigen negative
• Written informed consent prior to study entry

Exclusion criteria:

• Histologic transformation to diffuse, large cell lymphoma.
• History of more than one course of Rituximab
• Disease limited to single lymph node or single group of nodes
• Involvement of 25% of the intratrabecular marrow by bone marrow biopsy specimen.
• Active infection requiring IV antibiotics at the time of study entry
• New York Heart Association Class III/IV heart disease
• Prior chemotherapy, biologic, radiation or steroid therapy for NHL within 8 weeks
• Any prior radioimmunotherapy
• Prior history of malignancy other than lymphoma (except for treated basal cell, squamous cell skin cancer, in situ cervical cancer, or other cancer that is disease-free for 5 years)
• Known HIV infection
• Hepatitis B positive
• Known central nervous system involvement