The purpose of the present study was to predict the response of malignant lymphomas (MLs) to chemotherapy using technetium-99m methoxyisobutylisonitrile (Tc-MIBI) scan and to compare it with the predictive ability of P-glycoprotein (P-gp) expression, multidrug resistance-related protein (MRP) expression and other prognosis factors. Twenty-five ML patients were enrolled in this study prior to initiation of chemotherapy. Images were obtained 10 min after intravenous injection of Tc-MIBI, interpreted visually and the tumour-to-background (T/B) ratios calculated. Immunohistochemical analyses were performed on sections of the biopsy specimens to determine P-gp and MRP expression. Chemotherapy response was evaluated in the first 1-2 years after completion of chemotherapy. The mean T/B ratio of the 15 patients with a good response (3.3 +/- 0.6) was significantly higher than that of the 10 patients with a poor response (1.2 +/- 0.1). All 15 patients with a good chemotherapy response had positive Tc-MIBI scan results and negative P-gp and MRP expression. All 10 patients with a poor response had negative Tc-MIBI scan results and either positive P-gp or MRP expression. Other prognosis factors showed no significant difference in the incidence of good and poor responses. Tc-MIBI scan results represent P-gp or MRP expression more accurately than other prognosis factors and predict the chemotherapy response in ML patients.