ABSTRACT: The Brief Negative Symptom Scale (BNSS) grew out of a recommendation by the NIMH-sponsored Consensus Development Conference on Negative Symptoms that a scale based on contemporary concepts be developed. We assessed sensitivity to change of the BNSS in a trial of MIN-101, which showed efficacy for negative symptoms (PANSS pentagonal model) at daily doses of 32 and 64 mg/day. Using mixed-effects model for repeated measures, we examined change in BNSS total score and in the BNSS factors of anhedonia/avolition/asociality (AAA), and expressivity (EXP). Compared to placebo, the 64 mg group (N = 83) showed a significant decrease in BNSS total score (effect size d [ES] 0.56, p b 0.01) and both factor scores (AAA ES = 0.48, EXP ES = 0.46, p b 0.02 for both). Patients in the trial had minimal depression and positive symptom scores; covarying for disorganization, positive symptoms, or anxiety/depression did not cause a meaningful change in the significance of the BNSS total or factor scores in this group. The 32 mg group (N = 78) did not differ significantly from placebo (N = 83) on BNSS total score (ES = 0.33, p b 0.09), AAA (ES = 0.25, p b 0.20) or EXP (ES = 0.30, p b 0.12) scores. These results demonstrate the BNSS is sensitive to change.