Wilting of cotton plants infected with Phymatotrichum omnivorum is associated with an increased resistance to water flow in roots, crowns, and lower stems. A high molecular weight, pigmented substance was isolated from crowns of field-grown cotton plants infected with P. omnivorum but not from non-infected controls. The factor is water soluble and insoluble in methanol and weak acids. The molecular weight of the factor is over one million Daltons as determined by molecular exclusion filters. A 30 micrograms milliliter^-1 solution of the factor significantly reduced transpiration of excised 20-day-old cotton seedlings within 2 hours and induced wilting within 4 hours. Accumulation of the wilt inducing factor in xylem elements seems to be the most likely cause of the observed increase in resistance to water flow in roots, crowns, and lower stems of infected plants. Limitations of studies on the mechanism of wilting and the non-specificity of wilt inducing factors are discussed.