Transgenic mice that expressed antisense interleukin-3 (AS-IL-3) RNA were generated and exhibited either a B-cell lymphoproliferative syndrome or progressive neurologic dysfunction. Each syndrome occurred in the founder or progeny mice of three separate transgenic lines. The lymphoproliferative process involved the accumulation, within peripheral lymphoid organs, of B220+/slgM- pre-B cells that had immunoglobulin (Ig) genes predominantly in germline configuration and expressed lambda 5 and Rag-1 transcripts. Transgenic animals that developed neurologic dysfunction exhibited circling behavior that progressed to ataxia and terminal inanition. AS-IL-3 transcripts were detected in mature CD3+ T cells of asymptomatic transgenic animals, as well as in B220+/slgM- pre-B cells, and CD3+ T cells from animals with the lymphoproliferative syndrome. AS-IL-3 transcripts were also detected in the brains of both young asymptomatic transgenic animals and older transgenic animals with neurologic dysfunction. Decreased IL- 3 production from ConA-stimulated splenocytes was observed in asymptomatic transgenic animals. These observations suggest that this cytokine may have important roles in B lymphopoiesis and neurologic function.