Fusarium oxysporum f. sp. vasinfectum (FOV) Atk. Sny & Hans is a continuing threat to cotton production in the United States that warrants attention in plant breeding programs. Several developments concerning this pathogen (e.g. newly-recognized Australian FOV races and identification of FOV race 4 in California) highlight the need for additional research to provide improved host plant resistance to this pathogen. In order to assess the U.S. cotton gene pool and to study host plant resistance to FOV race 4, field and greenhouse evaluations were conducted in 2003, 2004, and 2005 on more than 150 Pima (Gossypium barbadense L.) and Acala and non-Acala Upland (G. hirsutum L.) entries. A population of 32 Pima recombinant inbred lines (RILs) and six F1 combinations of hybrids developed between susceptible and resistant entries were also evaluated. Pima cottons inoculated with race 4 developed more severe symptoms than the Acala and non-Acala Upland cottons, but some Acala and Upland cottons were severely infected. Germplasm with high levels of resistant to FOV race 4 was identified in some Pima entries. Resistance against FOV race 4 in Pima cottons was more complete than expected and may be determined by a single dominant major gene and one or more modifying minor genes, which may explain the trangressive segregation observed in some RILs. FOV resistance in Acala and non-Acala Upland cottons may be more complex and may be inherited in a quantitative manner by several major genes and minor modifying genes. This research identified new, improved resistant germplasm for release in the future for public incorporation into California cotton cultivars. In addition, this research provided information about the susceptibility of commercial cotton and improved germplasm that will allow growers to make informed decisions regarding which cotton cultivar to plant in fields infested with race 4. Development of highly resistant germplasm and genetic mapping of populations to develop and/or identify molecular markers to assist in breeding for FOV resistance in cotton are continuing.