DI-Leu16-IL-2 is more potent than the sum of its parts or higher doses of anti-CD20 antibody and free IL-2. Antitumor activities of medium-dose DI-Leu16-IL-2 (▪; 20 μg/mouse on days 7-11) and the corresponding doses of the individual antibody and IL-2 components (□; 16.7 μg DI-Leu16 and 3.3 μg IL-2 by intravenous on days 7-11) were compared to high-dose rituximab and subcutaneous IL-2 (⋄; 500 μg rituximab on day 7 and 10 μg IL-2 on days 7, 9, and 11), rituximab alone (♦; 500 μg on day 7), or PBS control (×). All treatment groups were significantly different from the PBS control and from each other (P < .05 or less) except for the 2 groups treated with both antibody and either intravenous or subcutaneous IL-2. These were not significantly different from each other.