The combination of Cis-dichlorodiammineplatinum (II) (CisDDPt) + 5-Fluorouracil (5-FU) was compared with two CisDDPt analogues + 5-FU [Iproplatin (CHIP) + 5-FU and Carboplatin (CBDCA) + 5-FU] for relative efficacy against advanced stage squamous cell lung tumors (LC-12) in Balb/c mice. At equitoxic dosages, the numbers of regressions and cures were similar for the three combinations (5-FU/CISDDPt 2/10 PR's, 2/10 CR's, 2/10 cures; 5-FU/CBDCA 1/10 PR's, 5/10 CR's, 3/10 cures; 5-FU/CHIP 1/10 PR's, 3/10 CR's, 3/10 cures). The tumor growth delay among the mice not cured was slightly superior in the 5-FU/CisDDPt regimen. All the agents were active singly against this tumor model. Based on these results, the substitution of CBDCA or CHIP for CisDDPt in a FU regimen did not offer a cytotoxic advantage. Because of different dose limiting toxicities for the platinum compounds the possibility exists that these analogues could be used in drug combinations in substitution for CisDDPt.