The use of the mouse spleen fragment culture system is extended to the production of antibodies to human lymphoblastoid cell lines. These antibodies were tested for reactivity against the immunizing cell line, and against a second cell line which had been derived from the same human blood sample. Many of the antibodies were found to discriminate between the 2 isogenic lines. These results demonstrate the potential of the mouse spleen fragment culture system to provide homogeneous reagents which detect distinguishing markers on closely related human cells.