Field studies were conducted in Arizona and California to evaluate the performance of glyphosate-tolerant lettuce and to determine the critical time of weed removal. Glyphosate was applied as a single or as a sequential application at 840 g ae/ha. Single glyphosate applications were made to lettuce at the two-, four-, six-, and eight-leaf stages. Sequential applications were made to lettuce at the two- or four-leaf stage followed by (fb) a second application 14 d after the first. Weed control efficacy, weeding times, and lettuce yield were all measured. Overall, glyphosate applied postemergence (POST) provided better weed control than the commercial standards bensulide or pronamide applied preemergence. Single glyphosate applications at the four-leaf stage and sequential applications at the two-leaf stage fb a second application 14 d later provided excellent control of most weeds, including redroot pigweed. Estimates of the critical time of weed removal were 26 to 29 d after emergence. Glyphosate treatments caused no adverse effects on lettuce. Lettuce head fresh weights in the glyphosate treatments were equal to or higher than those in bensulide or pronamide treatments. For crops such as lettuce, with few effective herbicides, the development of glyphosate-tolerant lettuce offers the opportunity to develop effective POST weed control programs.