The reniform nematode (RN), Rotylenchulus reniformis, is a serious threat to cotton production. Genetic resistance has been identified in diploid G. arboreum, but little is known about the resistance mechanism. The objective of this study was to describe the response of cotton roots to RN infection. The F1 and F2 generations from a cross between a highly resistant and susceptible accession of G. arboreum were evaluated to determine the number of genes involved. The data indicate that a single gene confers RN resistance, because the F2 generation segregates in a ratio of 3 resistant individuals for each susceptible one (÷2 <0.12). The assumption of a single gene controlling resistance would suggest that the gene effect is additive. This is supported by the observation that the mean of the F1 generation was not significantly different (p<0.5535) from the average of the two parental means. Host gene response to RN infection in G. arboreum was evaluated through cDNA-AFLP analysis 16-days after inoculation using a resistant and susceptible accession. After sequencing the differentially expressed transcripts, they were grouped according to their putative biological function suggested from homology searches in the GenBank Data bases (with BLAST). Cellular transport, cell cycle and DNA processing resulted in more transcripts in the susceptible accession than in the resistant one. We hypothesize that the transcripts associated with those processes may be related to syncytia formation. In the other hand, processes that may be involved in resistance mechanisms, such as cellular rescue, defense and transcription, had more transcripts in the resistant accession.