The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.