25 consecutive patients with advanced non-small cell lung cancer (NSCLC) were treated with high-dose epirubicin (HDE) 135 mg/m2 and etoposide 60 mg/m2 (days 1-3) every 3 weeks. 121 courses, (median 6, range 1-7), were administered and evaluable for toxicity: WHO grades III/IV leukocytopenia in 60/36 (80%) courses, thrombocytopenia in 18/6 (20%) and grades II/III anaemia in 31/6 (31%). Median (range) left ventricular ejection fraction (LVEF) fell from 63% (53-73, n = 25) to 60% (48-73 n = 16) after 5 courses (P < 0.02). 2 patients had a drop of more than 15% in LVEF with an epirubicin dose of 675 mg/m2. Apart from 1 patient who had tachycardia 6 months after the last course, no patient had congestive heart failure. There were 2 complete and 7 partial responses [total 9/25 (36%, 95% confidence interval: 18-57.5%)]. Median survival is 31.8 (4.3-75) weeks. Combination HDE and etoposide in NSCLC offers no advantage over HDE alone and is more toxic.