Skin tests were carried out with irradiated autologous tumor cells in patients with solid tumors (large-bowel carcinoma, gastric carcinoma, malignant melanoma, and breast cancer). With untreated cells, the skin reaction was negative or very weakly positive. A strong skin reaction, however, was elicited with cells of elevated membrane lipid microviscosity. This was induced by incorporation of cholesterol or, more effectively, by cholesterly hemisuccinate (CHS). A fair correlation was observed between the level of skin reaction with CHS-treated cells and the clinical stage of the tumor. It is suggested that rigidification of the cell membrane lipid layer exposes latent tumor-associated antigens, which enhances the cell-specific tumor immunogenicity. CHS-treated cells could therefore be of clinical value in active immunotherapy of human cancer.