In this report we have analyzed the effect of recombinant interleukin 2 (rIL 2) and rIL 2‐activated natural killer (NK) cells on the production of immunoglobulin isotypes by lipopolysaccharide (LPS)‐stimulated spleen cells from nude mice. We found that rIL 2 induced a dose‐dependent increase of IgG_2a secretion and a concomitant inhibition of the secretion of other Ig isotypes. The analysis of the phenotype of LPS‐ and LPS+rIL 2‐stimulated nude spleen cells showed the appearance of a Thy‐1⁺asialo GM‐1⁺slgM⁻CD3⁻CD4⁻CD8⁻ cell population in the presence of rIL 2. A population with a similar phenotype was generated upon stimulation of spleen cells from nude mice with rIL 2 alone. These cells lysed YAC‐1 cells, did not contain the α or γ transcripts encoding the corresponding T cell receptor chains and are therefore NK cells activated by rIL 2. In co‐culture experiments, these cells selectively increased the secretion of IgG_2a by LPS‐stimulated splenocytes from nude mice. The IgG_2a induction triggered by rIL 2‐activated NK cells, as well as that triggered by rIL 2, were blocked by an anti‐interferon γ monoclonal antibody. Thus, rIL 2 activated‐NK cells enhance the production of IgG_2a by secreting interferon‐γ.