The initial site of disease relapse was identified for 79 patients with metastatic renal cell cancer (RCC), melanoma, colon cancer, or non-Hodgkin's lymphoma (NHL), who had achieved partial or complete responses to one of five IL-2-based immunotherapy regimens. The initial site of relapse was evenly distributed between pre-existing sites of disease (33%), new sites of disease (38%), or both (29%). There was no difference in the distribution of recurrences between patients with partial or complete responses. Fifty-one patients with prior complete or partial responses were retreated with additional IL-2-based therapy following tumor progression. Five of 51 patients retreated following relapse developed new partial responses. There were no complete responses. Three patients with NHL were retreated with IL-2 and LAK cells and all achieved a second response, while only 2 of 48 patients with other histologic diagnoses reresponded. It is concluded that after a partial or complete response to IL-2-based immunotherapy, patients who relapse do so equally at new and pre-existing sites of disease. A response to retreatment following tumor progression may be attained in patients with NHL, while a new response is unlikely for patients with melanoma and RCC.