Immunological studies are presented on a patient with a long clinical history suggesting the existence of a tumor‐specific immune response. His tumor, first considered benign, progressed to a highly malignant osteosarcoma. Cell‐mediated immune reactivity against biopsy cells and against tumor extract was detected in vitro by the autologous tumor stimulation test (ATS) and in vitro by the skin test. In one ATS‐test with tumor extract, blastogenesis of T‐cells was demonstrated. The amount of Ig(s) in consecutive biopsies increased. Biopsies taken in the later period of the disease stimulated only after trypsin treatment. This stimulation was inhibited by autologous serum or acid eluate of the biopsy. The inhibitory factor in the serum was not intact immunoglobulin. Blood lymphocytes did not show a discriminatory or disease‐related cytotoxicity, either directly or after co‐cultivation with the tumor material. Lymphocytes isolated from one biopsy were non‐reactive in both the ATS and the cytotoxicity test.