We have investigated the involvement of interleukin 6 (IL-6), a growth-regulatory molecule for vascular smooth muscle cells (SMC), in the development of atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits. In in situ hybridization analysis, quite low levels of IL-6 mRNA were expressed in 'quiescent' SMC cultured from WHHL rabbits; however, high levels of IL-6 mRNA were induced in SMC exposed to 10% fetal bovine serum (FBS), suggesting that growth-stimulated SMC themselves can synthesize IL-6. In in vivo WHHL aortae, transcripts for the IL-6 gene were clearly observed in the fibrous plaques. These findings support the premise that IL-6 is an important autocrine and/or paracrine regulator of SMC proliferation and of pathogenesis of atherosclerosis in this animal model.