The ability of technetium-99m tetrofosmin (Tc-TF) scan to predict chemotherapy response in malignant lymphomas (ML) was compared with the predictive ability of P-glycoprotein (Pgp) and multidrug resistance related protein (MRP) expression. Before chemotherapy, 25 ML patients were enrolled in this study. Scans were performed 10 min after intravenous injection of Tc-TF. Immunohistochemical analyses were performed on ML specimen sections to evaluate Pgp and MRP expression. Chemotherapy response was evaluated in the first 1-2 years after completion of chemotherapy. Based on Tc-TF scan results, the mean tumor-to-background (T/B) ratio of the 15 patients with good response (3.23 +/- 0.56) was significantly higher than that of the 10 patients with poor response (1.18 +/- 0.11). All 15 patients with good response had positive Tc-TF scan results but negative Pgp and MRP expression. All 10 patients with poor response had negative Tc-TF scan results but positive Pgp or MRP expression. No significant differences in the incidences of good and poor response results were found for patients with Hodgkin's disease versus non-Hodgkin's lymphoma, with stage I-II versus stage III-IV, with age > 40 versus age < or = 40 years, or with B symptoms versus without B symptoms. Tc-TF scan results, which may represent either Pgp or MRP expression, accurately predict chemotherapy response in patients with ML.