Staple is the first true over-the-top herbicide that controls broadleaf weeds without causing excessive cotton injury. Earlier research suggested that Buctril-tolerant cotton cultivars (BXN 57 and 58) may be more sensitive to Staple than other cultivars. Experiments were conducted to compare weed control and cultivar sensitivity with Staple herbicide. The weed control experiment was conducted in 1994 and 1995 on a silt loam soil. The standard herbicide programs included soil-applied herbicides followed by three post-directed applications (3 inch, 10 inch, and layby). The comparison treatments included soil-applied herbicides followed by Staple 1.0 oz ai/A early over-the-top (EOT). The EOT application was followed by either one post-directed (layby) or two post-directed (10 inch and layby) applications. Programs that replaced either the early post-directed (EDIR) or both the EDIR and late post-directed (LDIR) applications with an EOT application of Staple provided equal control of pigweed, entireleaf morningglory, velvetleaf, and prickly sida when compared to the standard herbicide programs. But, when both the EDIR and LDIR applications were replaced with Staple EOT, control of pitted morningglory decreased. When Cotoran preemergence was replaced with 0.5 oz ai/A Staple in the soil component, broadleaf signalgrass control decreased regardless of the postemergence program. Three cotton cultivar sensitivity experiments were conducted in 1995 (two in Louisiana and one in Arkansas) and compared injury from four Staple treatments on the cultivars Coker 315, BXN 57, BXN 58, Stoneville 132, Stoneville 474, DPL 51, DPL 5409, DPL 20, and Suregrow 501. The Staple treatments included 1oz ai/A PRE followed by 1 oz EOT, 1 oz EOT, 2 oz EOT, and an untreated check. Minimal injury was observed in both Louisiana experiments, but a high level of injury was observed in the Arkansas experiment. In the Arkansas experiment, BXN 57 and BXN 58 were more sensitive to the sequential treatment than other cultivars, and there was a trend for BXN 58 and Stoneville 132 to be more sensitive to EOT applications than the other cultivars. This research indicates that Staple has the potential to replace one, or possibly two, post-directed applications, depending on weed populations. And, the BXN cultivars can express more Staple injury than other cultivars under some conditions.