Assessment of response to therapy in patients with lymphoma involving bone can be difficult. Of the scintigraphic techniques available, Tl-201 may be the most ideal radiopharmaceutical because it reflects tumor burden more accurately than either Tc-99m MDP or Ga-67 citrate. We compared serial Tl-201 and Ga-67 citrate scintigraphs (24 studies, 12 pairs) in assessing the response to therapy in three patients with non-Hodgkin's lymphoma involving bone. In two patients who demonstrated a complete remission, uptake of Tl-201 diminished more rapidly and returned to normal earlier than did Ga-67 citrate. Tl-201 did not show tumor recurrence in the one patient with lesions shown to be Tl-201 negative at baseline. Serial studies using Tl-201 may be superior to Ga-67 citrate in the evaluation of lymphoma involving bone provided that Tl-201 avidity is demonstrated on baseline studies.