Small-cell lung cancer (SCLC) is a disseminated disease regardless of our ability to document all sites. Chemotherapy is thus the cornerstone of treatment. There are multiple active single agents, resulting in many combination chemotherapy regimens. Optimal combinations are probably derived from the use of synergistic drug interactions. A three drug combination of doxorubicin (Adriamycin), cyclophosphamide, and etoposide (ACE) has been used at the University of Maryland Cancer Center (UMCC) for more than a decade in sequential studies. Two hundred four patients, 143 men and 61 women, were treated on these studies. Eighty-five had limited disease (LD) and 119 had extensive disease (ED). The complete response (CR) frequencies were 65% and 43% for LD and ED, respectively, and the median survivals were 15 and 9.5 months, respectively. Twenty-two percent of the LD patients were alive at 2 years. To improve upon response or survival, and because of synergy, cisplatin was added to ACE (PACE). PACE chemotherapy was administered in two studies--study 1 at UMCC for both LD and ED, and study 2 by Cancer and Acute Leukemia Group B (CALGB) for ED only. Preliminary review suggests that CR frequencies for LD (53%, study 1) and ED (44%, study 1; 37%, study 2) were similar to prior studies, but median survivals (LD, 18+ months, study 1; ED, 15 months, study 1, 10.5 months, study 2) appears superior to previous studies. However, PACE is more toxic than ACE. Further studies of PACE are needed to assess if the additional toxicities are warranted.