A large-scale trial of HLB-tolerant citrus cultivars is addressing the need of Indian River growers to identify the best rootstocks and scions for growing fresh fruit. The project has two objectives: (i) Assess the performance of new grapefruit cultivars with selected rootstocks; and (ii) Evaluate the influence of UFR and other rootstocks on grapefruit scion development in comparison to legacy/standard rootstocks. There are two trials: Trial 1) 18 grapefruit cultivars on three rootstocks; Trial 2) 32 rootstocks with `Ray Ruby’ grapefruit as the scion. The final 90 grapefruit trees on UFR-8 rootstock are scheduled to be planted in March-April 2022, which will bring the total number of trees with grapefruit scions to 2,741. Control-release polycoated fertilizer was applied appropriately in February 2022. All trees were treated as needed with appropriate agrochemicals to manage canker, Asian citrus psyllids, mites, and citrus leafminers. One night of subzero temperatures for a short period caused slight freeze damage to many trees, but the trees are expected to recover fully. No trees died due to the subzero temperatures. Trunk diameter and canopy volume were measured on the three middle trees in each experimental plot in October 2021 to assess tree size. At the time, there were significant differences among scion/rootstock combinations. In Trial 1, `Pummelette UF-5-1-99-2′ grapefruit on US-942 was 6X larger (395.5 ft3) than `US 1-83-179′ grapefruit hybrid on US-942 (70.6 ft3). In Trial 2, grapefruit on UFR-15 was 3X larger (314.3 ft3) than on UFR-17 (123.6 ft3). Many trees produced fruit. Size, color and taste of fruit varied among rootstock/scion combinations. No fruit data were collected because a tree’s first crop is not indicative of future production. Long-term evaluation is needed to identify the most promising scions and rootstocks to determine their profitability and capability of meeting grower and market needs. HLB is spreading in the study grove and visual blotchy mottle symptoms in the canopy are increasing. Leaf samples for quantifying CLas titer were collected in September 2021 and sent to Southern Gardens for analysis. Trees that are CLas-free (ct values >38) and CLas-infected and symptomatic (ct values of 26-32) can be found in the same plots, but many symptomatic trees are developing vigorous canopies. The incidences of Asian citrus psyllids (ACP), Diaprepes root weevils, whiteflies, leafminers, and citrus canker were low during the reporting period, probably due a decrease in temperatures and relative humidity, which reduces flush emergence and slows pest activity. Canker damage is noticeable but not uniform; it is especially significant on `Ray Ruby’ grapefruit trees. Nevertheless, tree growth has not been significantly affected by these pests due the timely applications of agrochemicals. Results of the study were presented at the annual Florida Citrus Show in January 2022 in Fort Pierce, FL by graduate student Martin Zapien.