Testing of new drugs in small-cell lung cancer is definitely necessary for the development of agents that might be effective against this tumor. However, testing such drugs in previously untreated patients with a good performance status (PS) may give rise to ethical problems. When previously treated patients are used in testing, potentially effective agents could well elude discovery. Patients who are not eligible for "standard" combination chemotherapy, e.g. untreated patients with a poor PS, may be suitable for testing of new drugs. To evaluate the potential usefulness of such patients in the testing of new agents, we evaluated an effective drug (etoposide) at a relatively nontoxic dose in a group of 14 patients with a PS of 4 (WHO). Oral etoposide resulted in a response in only 3 cases, whereas 5 subjects died of therapy-related toxicity. We conclude that previously untreated patients with a poor PS are not suitable candidates for the testing of new drugs.