Combination chemotherapy has been used widely in the treatment of inoperable adenocarcinoma of the lung (ACL), but without uniform success. This review summarizes current knowledge of combination chemotherapy in ACL, with the aim of establishing critical background material for future studies. Not all the numerous combinations applied in non-randomized studies have produced response rates above 20% when evaluated in randomized trials. This holds true for the following regimens: cyclophosphamide + lomustine + methotrexate (response rates 14%-38%), hexamethylmelamine + doxorubicin + methotrexate (13%-32%), methotrexate + doxorubicin + cyclophosphamide + lomustine (13%-24%), cyclophosphamide + doxorubicin + cisplatin (0-36%), cyclophosphamide + bleomycin + cisplatin (20%), mitomycin C + vinblastine + cisplatin (26%-33%), cyclophosphamide + doxorubicin + etoposide + cisplatin (29%) and vindesine + cisplatin (33%). None of these combinations has been shown to be clearly superior to single-agent treatment. Nor has any specific regimen been shown to have clear advantages over other active combination chemotherapy regimens or over the sequential administration of either single agents or combined treatments. The prognosis for patients with inoperable ACL remains dismal. None of the studies considered in this review revealed median survival times exceeding 47 weeks. High priority should therefore be given to the identification of new compounds with significant activity against ACL.