Our purpose was to study the feasibility of determining individualized chemotherapy regimens by in vitro drug sensitivity testing (DST) for patients with limited-stage small cell lung cancer (SCLC) and to evaluate patient response and survival. Fifty-four previously untreated patients with limited-stage small cell cancer were studied. Fresh tumor specimens for DST were collected, when possible, from patients' biopsies before the start of treatment. The differential staining cytotoxicity assay was used to determine the in vitro sensitivity of the tumor cells to different drugs. From these results, an in vitro best regimen (IVBR), a three-drug combination of previously proven efficacy of seven active drugs in SCLC, was selected. Patients were initially treated with four cycles of etoposide/cisplatin and concurrent radiotherapy. This was followed by four cycles of either individualized chemotherapy regimens based on the results of DST or, when DST results were not available, four cycles of vincristine, doxorubicin, and cyclophosphamide. Eighteen patients (33%) underwent biopsy procedures that provided tissue specimens for DST. The biopsy specimens contained tumor cells in 16 of 18 patients. The median duration from diagnosis to start of treatment was 22 days (range, 4-58 days) for the 18 patients who underwent elective thoracic biopsies compared to 21 days (range, 2-74 days) for members of the group that did not (P2 = 0.58). Time from thoracic biopsy to initiation of chemotherapy was a median of 4 days (range, 2-22 days). DST was done in 10 patients, and IVBR was administered to 8 patients. The median actuarial survival of 8 patients treated with their IVBR was 38.5 months compared to 19 months for the 46 patients treated with empiric chemotherapy. Selection of individualized chemotherapy regimens is labor intensive but feasible in limited-stage SCLC. Treatment with an individualized IVBR in our patients was associated with prolonged patient survival; however, because of the nature of our study design, other factors could have affected the results.