The ability of Adriamycin (AD) to enhance the known in vitro and in vivo tumoricidal effects of photodynamic therapy (PDT) on the H-MESO-1 human malignant mesothelioma cell line was investigated. In vitro cytotoxicity was determined by incubating H-MESO-1 cells in microtiter plates (2 x 10(5) cells/well, 6 wells/group) with the photosensitizer Photofrin II (PF) and varying concentrations of AD (0, 2.5, 5.0, and 10.0 micrograms/ml) for 24 hr followed by exposure to gold vapor laser light (GVL) at a fluence of 6000 J/M2. [3H]Thymidine (1 microCi) was added to each well 24 hr after treatment. Cells were harvested and counted for thymidine incorporation 24 hr later. PDT alone resulted in a decrease in thymidine incorporation of 23% while the addition of AD to PDT at AD concentrations of 2.5, 5.0, and 10.0 micrograms/ml resulted in decreases of 62, 85, and 69%, respectively (P = 0.005) as compared to untreated controls. H-MESO-1 tumor bearing nude mice (n = 5) were injected ip with PF (5 mg/kg) and AD (5 mg/kg) 24 hr prior to illumination of the tumor site with GVL (120 J/cm2). Control groups (n = 5) received PDT, AD, and/or GVL alone. Tumor surface area was measured as the product of the greatest perpendicular dimensions every 5 days for 30 days. Administration of PDT without AD resulted in a decrease in tumor surface area of 50% on Day 10 with regrowth of tumor by Day 30 while AD alone with or without GVL had no impact on tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)