The phytotoxicity of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), 1,1-dimethyl-3-(α,α,α-trifluoro-m-tolyl)urea (fluometuron), 3-(hexahydro-4,7-,methanoindan-5-yl)-1,1-dimethylurea (norea), and 2,4-bis(isopropylamino)-6-(methylthio)-s-triazine (prometryne) to cotton (Gossypium hirsutum L., var. Acala 4-42) was compared. Warburg experiments indicated that fluometuron and norea inhibited photosynthesis in isolated leaf disks to a much smaller extent than did diuron and prometryne. When the plants were grown in solution culture, diuron and prometryne were much more phytotoxic to cotton than fluometuron and norea, whereas when grown in soil, prometryne was the least phytotoxic, followed by norea, fluometuron, and diuron. Results of experiments on root vs. shoot uptake showed that all four herbicides entered the cotton seedlings through the roots, and no injury occurred to cotton when the compounds were applied to the shoot zone only. Norea and fluometuron were much more leachable than prometryne and diuron. These results indicate that depth protection in the soil, in addition to translocation and metabolism, might account partially for the tolerance of cotton to preemergence application of the tested herbicides.