These analyses of the COMBINE Study were designed to examine the effects of naltrexone among African Americans during the course of the 16-week treatment. Participants (total n=100; 70% male) who received naltrexone during the 16-week treatment trial (n=51) were compared to those who received placebo (n=49), controlling for acamprosate and behavioral intervention. Results did not support the efficacy of naltrexone on percent days abstinent, time to first heavy drinking day, and global clinical outcome in this subsample of African Americans. These results suggest that further work is needed to test naltrexone, as well as other medications, in this population and to identify treatment responders via genetics or other psychosocial predictor variables. Implications for pharmacogenetic studies of naltrexone are discussed.