The aim of this study was to investigate the relationship between Tc-99m-sestamibi accumulation in tumors and response to chemotherapy in children with untreated malignant lymphomas. Methods: Twenty-four children with malignant lymphoma (16 with Hodgkin's disease and 8 with non-Hodgkin's lymphoma) were studied with Tl-201 and then with Tc-99m-sestamibi scintigraphy before any therapeutic intervention. Visual and quantitative interpretation of Tl-201 and Tc-99m-sestamibi scans were performed. Visual uptake scores greater than or equal to 2+ were considered positive studies for Tl-201, and Tc-99m-sestamibi scintigraphy. Remission rates were evaluated at the end of induction therapy; patients were then followed clinically for 1-2 yr. Results: All 17 patients who had positive (99mT)c-sestamibi scans subsequently had a complete response to chemotherapy; all seven patients who had negative Tc-99m-sestamibi scans subsequently had partial or no response to chemotherapy, irrespective of the lymphoma type. The mean tumor-to-background ratios of patients with complete response and with partial or no response were 1.395 +/- 0.2 and 1.031 +/- 0.05 (p = 0.0002), respectively. Thallium-201 scintigraphy results were not related to the response to chemotherapy. Conclusion: Technetium-99m-sestamibi scintigraphy can provide information predicting the response to chemotherapy in patients with malignant lymphoma.