The purposes of this study were to predict the chemotherapy response of untreated malignant lymphomas (ML) using a technetium-99m tetrofosmin (Tc-TF) scan and to compare Tc-TF results with P-glycoprotein (Pgp) expression. Before undergoing chemotherapy, 25 patients with ML were enrolled in this study. Tc-TF scan was performed 10 min after intravenous injection of Tc-TF. Immunohistochemical analyses were performed on multiple sections of ML specimens to evaluate Pgp expression. The chemotherapy response was evaluated in the first 1-2 years after the completion of treatment. The mean tumor-to-background ratio of the 15 patients with good responses (3.23+/-0.56) was significantly higher than that of the ten patients with poor responses (1.18+/-0.11). All of the 15 patients with good responses had positive Tc-TF scan results, but negative Pgp expression. Among the ten patients with poor responses, all had negative Tc-TF scan results, but six had positive Pgp expression and four had negative Pgp expression. Significant differences in the incidences of good and poor responses were found between patients with positive Tc-TF scan results and patients with negative Tc-TF scan results and between patients with positive Pgp expression and patients with negative Pgp expression. No significant differences in the incidences of good and poor responses were found between Hodgkin's disease patients and non-Hodgkin's lymphoma patients, stage I-II patients and III-IV patients, patients aged >40 and patients aged < or =40 years, and patients with and without B symptoms. Compared with other prognostic factors, Tc-TF scan results and Pgp expression more accurately predict the chemotherapy response in patients with ML.