The intensity of treatment and the extent of restaging necessary to document the level of response to therapy in patients with non-Hodgkin lymphoma (NHL) remains controversial. One hundred patients with advanced non-Hodgkin lymphoma were randomized to treatment with cyclophosphamide, vincristine, plus prednisone or cyclophosphamide, doxorubicin, vincristine, plus prednisone combination chemotherapy. After induction therapy sequential noninvasive restaging including lymphangiogram and 67gallium scan yielded 33 patients in clinical complete remission and 38 patients in partial remission. Twenty of these 38 patients in partial remission had complete normalization of all clinical and chemical tests ("apparent" clinical partial remission); however, lymphangiogram, gallium scan, abdominal sonogram, or abdominal CAT scan remained abnormal. In these 20 patients in "apparent" clinical partial remission, exploratory laparotomy was performed to further assess disease status. Laparotomy revealed evidence of residual disease in only four patients (20%). When correlated with the laparotomies the accuracy of repeat lymphangiograms and gallium scans was 17% and 50% respectively. Thus, restaging lymphangiogram and gallium scan in NHL patients in "apparent" clinical partial remission are inaccurate, and "second look" operations are recommended for accurate appraisal of response to therapy. The assessment of true complete remission should help define the role of aggressive treatment.