SSA/Ro and SSB/La are soluble cellular proteins to which antibodies are frequently produced in patients with Sjögren's syndrome and systemic lupus erythematosus. In this investigation, we examined anti-SSA/Ro and anti-SSB/La staining patterns on synchronized WiL2 cells and mixed lymphocyte culture cells using monospecific antisera. In addition to its presence in the nucleoplasm, the SSB/La antigen was highly concentrated in the nucleolus of cells during the late G1 and early S phase and is thus cell cycle-related. In contrast, the SSA/Ro antigen was found to be independent of cell cycle, showing a nuclear speckled pattern in all phases. Blocking experiments indicated that free SSB/La is responsible for the nucleolar staining, whereas the combination of both SSA/Ro and SSB/La determines the nucleoplasmic speckled staining pattern.