ST-L1 is a cell line established from lung explants from a normal ST/a mouse. The ST-L1 cells have undergone spontaneous malignant alteration in vitro. The cells were rejected after inoculation into syngeneic immunocompetent hosts, and a syngeneic humoral immuneresponse against the ST-L1 cells has been detected. The specificity of this humoral response was investigated. The syngeneic response to ST-L1 was characterized by indirect immunofluorescence tests and by immunoprecipitation of radiolabelled cells and of a C-type virus produced by the cell lines. The specific anti-ST-L1 reactivities were found to be directed against the envelope glycoprotein of an endogenous C-type virus expressed by the antigenic cell line.