Total growth of transplanted human or rodent tumors in the subrenal capsule of mice was much improved by treatment with cyclosporine (CSA, cyalosporin A). Tumor size increased rapidly between days 6 and 12 after implantation. CSA injected on days 1-5 or 2-8 prevented tumor regression. In contrast, immulolQgic regression occurred after 6 days in absence of the drug. Seyeral assays for growth in vitro of clonogenic human tumor cells have been developed, and these may be useful for certain tumor types. However, results with these methods have not been easily reproducible, and many human tumors give cloning efficiencies too low to evaluate (2). Moreover, clonogenic assays do not provide a system to study (i) toxicity of drugs to normal tissues, (ii) host responses to tumor growth, or (iii) localization or activation of drugs and other agents in tumor vs. normal tissues. Monoclonal antibodies and angiogenesis inhibitors are two promising therapeutic approaches that cannot be evaluated by clonogenic assays.Subcutaneous implantation of human or rodent tumors into athymic nude mice is an alternative method for investigations of tumor-host interactions and new treatment strategies. This technique, although generally usable, is time-consuming, and nude mice and the facilities necessary to maintain them are expensive enough to limit its practicality (3).The subrenal capsule (SRC) assay developed by Bogden and coworkers (3, 4) permits precise in situ measurement of transplanted human tumors by use of a stereomicroscope with an ocular micrometer. Beneath the transparent renal capsule of mice is an advantageous site for delivery of nutrients, drugs, or other substances to the implanted tumor. In contrast to the subcutaneous sit', which often requires weeks or months for appreciable tumor growth, in nude mice the SRC assay can quantify small changes in tumor size after 6-12 days.With normal mice, a 6-day protocol is used for the SRC assay; this is an attempt to avoid the period of greatest immunologic regression, which occurs 6-12 days after tumor implantation (4). A comparison (5) of the SRC assay with a human tumor cloning method (bilayer soft agar) developed by Hamburger and Salmon (6) showed that the SRC method gave about twice as many evaluable assays. This observation suggests that the subcapsular site is a more favorable medium for growth of solid human tumor explants than is soft agar. Initial studies with fresh surgical explants of human cancers in the 6-day SRC assay also indicate a high success rate for several common human tumors, exceeding 80% for breast, ovarian, lung, and colon cancers (7).Because of the rapid end point and economy of the SRC assay in normal mice, these initial studies suggested that it could be useful for other investigations of human cancer biology or therapeutic strategies. However, two major problems prevent such applications. (i) Minimal growth of primary human tumors limits the capacity of the 6-day assay for discrimination of drug treatments. (ii) Inflammatory responses of immunoc...