Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine capable of inducing smooth muscle activation and leukocyte recruitment in restenosis and atherosclerosis. Our present study investigated the expression of IL-1 beta, IL-1 receptor antagonist (IL-1ra), and IL-1 receptor (IL-1RI and IL-1RII) mRNA in carotid artery after balloon angioplasty using semiquantitative reverse transcription/polymerase chain reaction (RT/ PCR) and Northern analysis. Time course studies revealed that IL-1 beta mRNA was rapidly induced at 6 h (30-fold increase over control, P < 0.001) post balloon injury and diminished to basal levels at 24 h. The increased expression of IL-1ra mRNA was delayed, reaching a peak at 24 h (400-fold increase, P < 0.001) and sustained up to 14 days. The expression of IL-1RII mRNA was remarkably similar to that of IL-1 beta, whereas the IL-IRI (the signaling receptor) mRNA expression was delayed (significantly induced at day 1; 14.2-fold increase, P < 0.01) post balloon injury. Immunohistochemical studies revealed a strong induction of IL-1 beta in the area with actively proliferating and migrating smooth muscle cells (i.e., in the inner medial layer at day 1 and in neointima at day 14 after balloon injury). The differential but concomitant expression of IL-1 beta, IL-1ra, IL-1RI, and IL-1RII mRNAs after balloon angioplasty suggests that each of these IL-1 system components may play a distinct role in neointima formation.