Multilamellar liposomes administered into body cavities tend to remain for a prolonged period of time inside the cavity and are mainly drained by the lymphatic system. This may enhance the therapeutic effects of drugs incorporated in liposomes inside the cavity and in the regional lymph nodes. L-NDDP is a lipophilic cisplatin analogue which has been incorporated in multilamellar liposomes for its administration in humans. L-NDDP is not cross-resistant with cisplatin in several in vitro and in vivo systems. In a Phase I study in humans by intravenous administration, L-NDDP was well tolerated and non-nephrotoxic. The dose limiting toxicity was myelosuppression. The easy access to the pleural cavity of patients with malignant pleural effusions provides a unique opportunity for testing the pharmacological effects of cytotoxic agents against human tumor cells ex vivo. We propose to conduct a Phase I-II clinical study of L-NDDP by intrapleural administration in patients with malignant pleural effusions. The objectives of the study are: 1) to determine the maximum tolerated dose, spectrum of toxicity, and antitumor efficacy of L-NDDP administered into the pleural space in patients with malignant pleural effusions, 2) to correlate tumor response with Pt and Pt-DNA levels in malignant cells from the pleural cavity and peripheral leukocytes after the administration of L-NDDP into the pleural space, 3) to study the pharmacokinetics of L-NDDP in plasma and pleural fluid, and 4) to determine the fate of multilamellar liposomes by nuclear imaging techniques after the administration of 99mTc labeled liposomes into the pleural space. The results of the study will indicate 1) the potential of L-NDDP and other liposome-entrapped antitumor agents in the treatment of malignant pleural effusions, and 2) the ability of liposomes infused into the pleural cavity to target the mediastinal lymph nodes. If significant mediastinal lymph node targeting is observed, agents such as L-NDDP may be particularly useful as a therapeutic tool for the treatment of mediastinal lymph node metastases, which are one the first sites of dissemination of lung tumors.