The root knot nematode (RKN, Meloidogyne incognita) is one of the destructive pests in the Southwest Cotton Belt of the U.S. This investigation was conducted to understand the genetic and molecular basis of RKN resistance in cotton. (1) Quantitative genetics: 12 genotypes including 7 susceptible (S) lines, 1 moderately resistant (MR) line, 3 highly resistant (R) lines derived from Auburn 623 and F1 between 33B and Auburn 634 were evaluated in the greenhouse for plant growth, RKN egg reproduction and root galling. RKN egg reproduction was highly positively correlated with galling index and both were highly negatively correlated with plant growth characteristics including plant height, number of leaves, and plant and root weight. Comparison between F1 and their parents in egg reproduction and galling revealed that the RKN resistance was partially dominant. The general combining ability played more important role than the specific combining ability in controlling the RKN resistance. (Euphytica, accepted). (2) Mendelian genetics: Five F2 populations using Auburn 634, its derived resistant line M-240, and Nem-X of unknown resistant source confirmed that the resistance is either controlled by one dominant gene or one dominant gene and one recessive gene. (2004 Proc. Beltwide Cotton Conf. p.1122-1124). (3) Disease resistance gene analogues: Degenerate primers designed from conserved motifs of known plant resistance gene products were used to amplify genomic DNA sequences from Auburn 634. A total of 165 clones were isolated and sequence analysis revealed 57 of the clones to be novel nucleotide sequences, many containing the R-protein nucleotide-binding site (NBS) motif. A cluster analysis was performed with resistance gene analogue (RGA) nucleotide sequences isolated in this study, in addition to 99 cotton RGA nucleotide sequences already deposited in GenBank. The cotton RGA nucleotide sequences were arranged into 11 groups and 56 sub-groups based on genetic distances. 61 pairs of RGA-STS (sequence-tagged site) sequence primers were designed from these groups and subgroups. A recombinant inbred line (RIL) population of cultivated tetraploid cotton was screened using RGA-STS primers that amplified polymorphic fragments between the two RIL parents. Nine RGA markers were mapped to homeologous chromosomes 12 and 26. (Theor. and Appl. Genet. 110: 237-243). (4) Molecular mapping: By comparing several pairs of near isogenic lines (NILs) with or without the Auburn source resistance, two RGA, two RAPD, and two AFLP markers were identified to be consistently polymorphic between the NILs. The two RAPD markers and one of their converted STS markers classified 23 resistant and 8 susceptible germplasm into three groups that reflected their resistance origins. These RKN resistance-associated markers will be useful in germplasm screening for RKN resistance and map-based cloning for RKN resistance genes. (Crop Sci., internal review). (5) Field testing: four pairs of NIL lines are being grown in a replicated field test in 2005 to evaluate the genetic effects associated with RKN resistance. (6) Gene expression: One pair of NIL is used to identify genes that are differentially expressed during RKN infection using cDNA-AFLP and microarray technology.