Tilapia lake virus (TiLV) is a lethal virus impacting farmed tilapia ( Oreochromis spp.). The virus was identified in 2014 and its emergence has resulted in substantial economic losses to the global tilapia industry. Given the lack of treatment options currently available, selective breeding for increased disease resistance may be a viable option for reducing the impact of this pathogen . Therefore, this study was initiated to phenotype Nile tilapia (O. niloticus ) families for resistance to TiLV and determine its additive genetic variation and heritability. Fish from the eleventh generation of the Spring Genetics Nile tilapia breeding program with nucleus operations in Homestead, Florida, US, were used for this study . A total of 142 full-sib families (mean weight, 142.3 g) were included in the challenge with on average 17 fish per family (range, 4 to 20) . All fish were challenged at the USDA-ARS AAHRU with TiLV via intraperitoneal injection with a viral dose corresponding to 2.25 × 104 TCID 50 fish-1 and placed into a single 5,550 L tank. Mortality data on each individual fish was collected for 21 days post challenge and a univariate animal linear model was used for quantitative genetic analyses. The a ccumulated mortality at the end of the experiment was 74.5% . The results revealed high variation in the mean survival of the families challenged with TiLV (range, 0% to 95 %). The additive genetic effect for survival to TiLV was significantly different from zero (P < 0.001; log-likelihood ratio) and the estimated heritability was h2 = 0.29 ± 0.1 . The results demonstrated moderate additive genetic variation in resistance to TiLV and suggest promise in genetic improvement of tilapia for resistance to this virus by selective breeding. Genomic analyses are pending to evaluate the potential for genomic or marker assisted selection. In the next generation, families will be produced by assortative mating (high and low estimated breeding values) and challenged to confirm the heritability of resistance to TiLV. The end goal is the production of a high performing strain of tilapia with disease resistance for the global tilapia industry.