We have shown previously that RNA and nucleotides strikingly augment in vitro antibody (Ab) production to SRBC in B6 mice.1 This may indicate a possibility that nucleotides exacerbate the state of autoimmunity by further enhancing Ab production. Thus we examined effects of yeast RNA/nucleotides on Ab and immunoglobulin (Ig) production in response to specific antigens (Ag) and LPS, a polyclonal B cell activator, in normal and autoimmune-prone NZB mice. RNA enhanced in vitro Ab and IgM production to T-dependent Ag (TD-Ag) in normal mice but did not augment Ig/Ab production potentiated by LPS or TNP-LPS in both normal and NZB mice. B cells in NZB mice were already polyclonally activated as reported before producing Ig spontaneously, which was not further augmented by specific Ag stimuli or LPS irrespective to the presence of RNA. Spontaneous Ab production to SRBC observed in old NZB mice were not augmented by RNA either. However, RNA enhanced specific Ab production to TD-Ag even in NZB mice and potentiated the proliferation of NZB lymphocytes as comparatively as did in normal strains. Thus it is unlikely that RNA and nucleotides potentiate or facilitate polyclonal B cell activation.