The inverted repeats present in a genome play dual roles. They can induce genomic instability and, on the other hand, regulate gene expression. In the present study, we report the distribution and sequence features of recombinogenic long inverted repeats (LIRs) that are capable of forming stable stem-loops or palindromes within the human genome. A total of 2551 LIRs were identified, and 37% of them were located in long introns (largely > 10 kb) of genes. Their distribution appears to be random in introns and is not restrictive, even for regions near intron-exon boundaries. Almost half of them comprise TG/CA-rich repeats, inversely arranged Alu repeats and MADE1 mariners. The remaining LIRs are mostly unique in their sequence features. Comparative studies of human, chimpanzee, rhesus monkey and mouse orthologous genes reveal that human genes have more recombinogenic LIRs than other orthologs, and over 80% are human-specific. The human genes associated with the human-specific LIRs are involved in the pathways of cell communication, development and the nervous system, as based on significantly over-represented Gene Ontology terms. The functional pathways related to the development and functions of the nervous system are not enriched in chimpanzee and mouse orthologs. The findings of the present study provide insight into the role of intronic LIRs in gene regulation and primate speciation.