The presence of normal anti-CD20⁺ B cells does not diminish the antitumor activity of DI-Leu16-IL-2. The effect of prior implantation of normal human CD20⁺ B cells was tested in the same SCID/Daudi lymphoma model as described in “Materials and methods.” Groups of mice were treated with a single high dose of rituximab (diamonds; 25 mg/kg on day 7), a medium dose of DI-Leu16-IL-2 (squares; 1 mg/kg on days 11-15), the combination of both dosing regimens (triangles; rituximab on day 7 followed by DI-Leu16-IL-2 on days 11-15) or PBS alone (circles) on all dosing days. Half of the groups were injected intravenously with 4.5 × 10⁷ PBMCs on day 5 (open symbols) or received only PBS (filled symbols). B-cell engraftment was confirmed by measuring human antibody levels in the serum of all mice. All treatment groups were significantly different from the PBS control (P < .005 or less) and all different treatment modalities were significantly different from each other (P < .01 or less). There were no significant differences between groups receiving the same treatment but with or without human B-cell implantation.