An experiment was conducted at four locations in North Carolina during 1994 and 1995 to evaluate weed control, cotton yield, fiber quality, and net returns in no-tillage bromoxynil-tolerant cotton. The experiment focused on using bromoxynil or pyrithiobac sodium applied early POST over-the-top as alternatives to fluometuron plus MSMA applied early POST directed. Fluometuron plus MSMA was more effective than bromoxynil or pyrithiobac sodium on tall morningglory, large crabgrass, goosegrass, and broadleaf signalgrass. Bromoxynil and fluometuron plus MSMA were similarly effective on common lambsquarters, common ragweed, and eclipta and more effective than pyrithiobac sodium. Pyrithiobac sodium and fluometuron plus MSMA were similarly effective on smooth pigweed and Palmer amaranth and more effective than bromoxynil. Prickly sida control by bromoxynil and pyrithiobac sodium was equal to or greater than control by fluometuron plus MSMA. All early POST herbicides controlled pitted morningglory similarly. Regardless of the early POST herbicides used, fluometuron applied PRE and cyanazine plus MSMA applied late POST directed increased control of most weeds and increased cotton yield and net returns. Bromoxynil and pyrithiobac sodium effectively substituted for fluometuron plus MSMA only in systems that included fluometuron applied PRE and cyanazine plus MSMA applied late POST directed. Effects of herbicide systems on cotton fiber quality were minor.