Chemical defoliation of cotton (Gossypium hirsutum L.) in preparation for mechanical harvest can be difficult because of inconsistent response of plants to harvest-aid applications. Unsatisfactory harvest-aid performance is often blamed on environmental conditions, but proper selection of carrier volume and nozzle type may help to improve harvest-aid efficacy. The objective of this study was to determine the optimum combination of carrier volume and nozzle type for maximizing harvest-aid efficacy. Desiccation, defoliation, and regrowth were evaluated on cotton treated with tribufos or thidiazuron alone at carrier volumes of 47, 94, and 140 L ha-1 with flat fan, hollow cone, or air induction nozzles. In Alexandria, carrier volume did not influence defoliation; however, defoliation with hollow cone and flat fan nozzles was at least 6% higher than defoliation with air induction nozzles at all evaluation dates regardless of carrier volume. In St. Joseph, percentage defoliation increased as carrier volume increased, and defoliation with flat fan and hollow cone nozzles was similar and superior to that of air induction nozzles. Carrier volumes ≥ 94 L ha-1 provided at least 10% more defoliation than 47 L ha-1 in Jackson, and performance of hollow cone nozzles was superior to both flat fan and air induction. A conclusion that can be drawn from these data are that harvest-aid applications should be made with flat fan or hollow cone nozzles at carrier volumes of at least 94 L ha-1 to maximize efficacy; however, the influence of carrier volume and nozzle type seem to be greater at more northern latitudes where environmental conditions often limit the performance of harvest-aids. Air induction nozzles should not be recommended for cotton defoliation due to inconsistent and inferior performance; however, they should still be considered in drift sensitive areas.