Proteoglycans accumulate in lesions of atherosclerosis but little is known as to which factors regulate the synthesis of these molecules. Interleukin-1beta (IL-1beta) is a cytokine involved in vascular lesion development but it is not clear whether it has specific effects on proteoglycan synthesis by arterial smooth muscle cells (ASMC). Monkey ASMC were treated with IL-1beta and proteoglycan synthesis assessed using [(35)S]-sulfate and [(35)S]-Trans amino acid labeling. Four prominent size populations of proteoglycans, as determined by SDS-PAGE gradient gel electrophoresis, were observed in the culture medium and identified as versican, biglycan, decorin, and an unknown population that migrated to the gel interface. IL-1beta treatment decreased significantly the synthesis of versican, while increasing the synthesis of decorin, but having no effect on biglycan synthesis. Northern blot analyses confirmed this selective effect on versican and decorin mRNA transcripts. Nuclear run-on and RNA inhibition studies showed that decreased mRNA for versican was due to increased mRNA degradation and not to changes in transcription. In addition, IL-1beta increased the synthesis of the population of proteoglycans that separated at the SDS-PAGE gel interface. Chondroitinase ABC lyase digestion of this population revealed a complex of proteins composed of versican (350 kDa), an unidentified protein (215 kDa), and a 23 kDa protein identified by sequence analyses as serglycin. These data demonstrate that IL-1beta selectively downregulates versican synthesis by ASMC, while positively regulating the synthesis of other proteoglycans.