Pegylated-liposomal doxorubicin (Doxil™) is a form of liposomal doxorubicin in which the liposomes are coated with methoxypoly(ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, a longer half-life in blood, and a different toxicity profile than nonpegylated liposomes. A phase II study of Doxil™ in mesothelioma was performed. The initial dose per course was 55 mg/m2 every 4 weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 73 evaluable treatment courses in 15 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. Fourteen patients were evaluable for response; four of the 15 patients treated responded meaningfully. These data suggest that pegylated-liposomal doxorubicin has activity in mesothelioma, and that this treatment is associated with modest toxicity.