Three field  experiments were carried out in the Experimental Station, Faculty of Agric, Cairo Univ. during three seasons (1997, 1998 and 1999). Giza 75 variety was used in 1997 and Giza 89 in 1998 and 1999 to investigate the response of cotton plant to irrigation after different depletion levels of available soil moisture (40, 60 and 80 %) under three levels of NPK fertilizers to determine the best treatment of irrigation interval and fertilizer level which gives the highest yield and quality. Results obtained indicated that, irrigation and fertilizer levels, with one exception , had a significant effect on number of open bolls/plant and in-significant effect on boll weight at all seasons. Irrigation at 60 % ASMD and lower or recommended. NPK levels gave the highest seed and lint cotton yields. In general irrigation and fertilizer levels had no significant effect on lint properties in 1999 season and a significant effect with few exceptions in 1997 and 1998 seasons. Irrigation at 80 % ASMD gave the lowest value of W.C.U and the highest value of W.U.E. Low NPK fertilizer level gave the highest values of fertilizer use efficiency.