Interleukin-one alpha (IL-1alpha) is located in the stellate reticulum and its receptor, type I IL-1R (IL-1R), is present in the adjacent dental follicle. IL-1alpha may play a role in initiating tooth eruption because of its ability to enhance the gene expression in the dental follicle of putative tooth eruption molecules colony-stimulating factor-one (CSF-1). monocyte chemotactic protein-1 (MCP-1), and nuclear factor kappa B (NFkappa-B). To directly examine the effect of IL-1alpha and IL-1R on tooth eruption, we observed the times of tooth eruption in null mice devoid of the type I IL-1R gene. The results showed that the time of eruption in the null mice was delayed by 2 d for the first mandibular molar and 1 d for incisors as compared to wild type controls. Reverse transcription-polymerase chain reaction (RT-PCR) techniques confirmed the absence of the IL-1R gene in the null mice, but the genes for CSF-1 and NFkappaB were still expressed. Thus, a molecule(s) other than IL-1alpha also may enhance the expression of CSF- and NFkappaB in the dental follicle. Because there is a slight delay of tooth eruption in IL-1R null mice, IL-1alpha may normally play a role in eruption. However, eruption eventually can occur without the signaling from IL-1alpha.