We evaluated the usefulness of 99mTc-tetrofosmin (TF) scintigraphy in monitoring chemotherapy response in 31 inoperable lung cancer (LC) patients, 24 NSCLC and 7 SCLC. In all cases after 740 MBq 99mTc-TF i.v. injection both planar and SPECT images were acquired, before and after 3 cycles of chemotherapy; SPECT was analysed both qualitatively and semiquantitatively by calculating tumor/background ratio (T/B). Scintigraphic data were always related to CT findings, according to which patients were classified into 2 groups after therapy: responders (with >or=50% reduction in tumor size) and non-responders (with an increase or no change/no significant reduction in tumor size). Four patients were rechecked for the third time, during long-term follow-up. SPECT images, positive before therapy in all cases, were concordant with CT in assessing treatment response in 13/13 responders and in 18/18 non-responder patients, showing tumor reduction in the former and an increase or no change/no significant reduction in the latter. Planar imaging failed to give additional information but also led to disease down-staging in some cases. T/B ratio significantly decreased after therapy (1.67+/-0.39 vs. 3.02+/-0.87, p<0.005) in responders <or=1.9 in each patient except one with local disease progression at the third observation. No significant difference in T/B ratio was found in non-responders after treatment (2.11+/-0.65 vs. 2.13+/-0.60), with variable results in single patients, including a T/B ratio reduction in some cases, one of which with local disease remission at third observation. Moreover, pre-therapy T/B ratio was significantly higher (p<0.01) in responders than in non-responders. 99mTc-TF SPECT, but not planar, may be useful in monitoring the chemotherapy response in inoperable LC patients; the additional use of T/B ratio seems to give more accurate information and may be useful for treatment response prediction and for better evaluating disease progression or regression after therapy.