Active specific immunotherapy with liposomal vaccines targeted to the mucinous carcinoma-associated glycoprotein MUC1 have shown promising results in animal models. The aim of this phase I study was to evaluate the safety and immunogenicity of 2 dose levels of the MUC1 liposomal vaccine preparation BLP25. Patients with stage IIIB or IV non-small-cell lung cancer received either 20 microg or 200 microg of the liposomal BLP25 vaccine preparation. Injections were administered subcutaneously at weeks 0, 2, 5, and 9. Immunological responses to vaccination were measured by antibody production, cytotoxic T lymphocytes (CTL), and proliferative T-helper cells. Seventeen patients were entered on study; 12 patients completed the vaccination protocol. Two patients, 1 in each dose group, developed clinically insignificant grade 3 lymphopenia during the study. Nonhematologic toxicities were mild and self-limiting, and there were no significant long-term injection site reactions. Immunological assays revealed the generation of CTLs against MUC1-positive tumor cell lines in 5 of 12 evaluable patients. These patients did not have CTLs prior to receiving the vaccine. No significant humoral response to the vaccination was observed. No objective antitumor responses were observed. Of the 12 patients completing all the vaccinations, 4 had stable disease. Median survival time was 5.4 months in the 20 microg group and 14.6 months in the 200 microg group. In summary, the BLP25 liposomal vaccine was well tolerated and elicited a primarily cellular immune response in these lung cancer patients. This study forms the basis for further clinical exploration of the MUC1 liposomal vaccine, BLP25.