SummaryThe Toll/interleukin‐1 receptor (TIR) domain is found in one of the two large families of homologues of plant disease resistance proteins (R proteins) in Arabidopsis and other dicotyledonous plants. In addition to these TIR‐NBS‐LRR (TNL) R proteins, we identified two families of TIR‐containing proteins encoded in the Arabidopsis Col‐0 genome. The TIR‐X (TX) family of proteins lacks both the nucleotide‐binding site (NBS) and the leucine rich repeats (LRRs) that are characteristic of the R proteins, while the TIR‐NBS (TN) proteins contain much of the NBS, but lack the LRR. In Col‐0, the TX family is encoded by 27 genes and three pseudogenes; the TN family is encoded by 20 genes and one pseudogene. Using massively parallel signature sequencing (MPSS), expression was detected at low levels for approximately 85% of the TN‐encoding genes. Expression was detected for only approximately 40% of the TX‐encoding genes, again at low levels. Physical map data and phylogenetic analysis indicated that multiple genomic duplication events have increased the numbers of TX and TN genes in Arabidopsis. Genes encoding TX, TN and TNL proteins were demonstrated in conifers; TX and TN genes are present in very low numbers in grass genomes. The expression, prevalence, and diversity of TX and TN genes suggests that these genes encode functional proteins rather than resulting from degradation or deletions of TNL genes. These TX and TN proteins could be plant analogues of small TIR‐adapter proteins that function in mammalian innate immune responses such as MyD88 and Mal.