The La antigen recognized by certain lupus erythematosus autoantibodies was found to be predominantly associated with 7 S RNA in baby hamster kidney cells and human Raji cells, but not in HeLa cells where mainly the 7-2 RNA was associated with the La protein. In mouse myeloma cells (MPC-11) and mouse lymphoma cells (WEHI) that secrete immunoglobulins, equal amounts of 7 S and 7-2 RNAs were present in anti-La immunoprecipitates. The highly conserved 7 S RNA is a component of the signal recognition particle involved in protein secretion (Walter, P., and Blobel, G. (1982) Nature (Lond.) 299, 691-698), and its association with the La antigen appeared to be cell-type specific. Thus, it is possible that the La-7 S RNA association correlates with the abundance of 7 S RNA or with the secretory activity of the cell type.