To determine the maximum tolerated dose (MTD) of [I-131]tositumomab in patients with refractory/recurrent Hodgkin lymphoma (HL) and to preliminarily determine if [I-131]tositumomab has activity against HL and if positron emission tomography (PET) with 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]DG) performed 6 weeks post-therapy predicted 12-week response. Separate dose-finding studies were performed for patients with and without prior transplant. A single therapeutic total body radiation dose (TBD) of [I-131]tositumomab was administered. TBD was escalated/de-escalated based on dose-limiting hematologic toxicity (DLT) using a modified continual reassessment method. [F-18]DG-PET/CT scans were performed at baseline and 6 and 12 weeks post therapy. Twelve patients (nine classical HL, three lymphocyte-predominant [LP] HL) completed two dosing levels (n = 3 each) in the post-transplant (55 cGy, 79 cGy) and no transplant (75 cGy, 87 cGy) groups. Hematologic toxicities were common and transient. Twelve weeks after [I-131]tositumomab, 10 patients progressed and two with LPHL achieved complete response. [F-18]DG-PET/CT at 6 weeks post therapy appeared more predictive than CT at 6 weeks of a response at 12 weeks. Tositumomab and [I-131]tositumomab was well-tolerated in patients with relapsed/refractory HL. Complete responses in LPHL support a therapeutic effect in this subtype. Early metabolic response assessments by [F-18]DG-PET in HL after radioimmunotherapy appear to be more predictive than purely anatomic assessments.