Purpose: This study sought to determine the minimally detectable change (MDC) of sentence intelligibility for speakers with multiple sclerosis (MS) and Parkinson's disease (PD). Method: Speakers included 78 participants consisting of 32 neurologically healthy control speakers, 30 speakers with MS, and 16 speakers with PD. All speakers were recorded reading 11 sentences comprising the Speech Intelligibility Test (SIT), which were subsequently transcribed by inexperienced listeners. Percent correct scores were calculated for each sentence. An average percent correct score was also calculated for each speaker. The MDC at the 95% confidence interval was calculated using the following formula: MDC[subscript 95] = 1.96 × [square root]2 × standard error of measurement. Speakers were divided into operationally defined categories of severity, and MDCs were calculated for each category to permit comparison to MDCs reported for speakers with amyotrophic lateral sclerosis (ALS). Kruskal-Wallis tests were conducted to compare MDCs between groups and severity categories. Results: The average MDC95 for control speakers was 5.53% (range = 3.21%-7.47%) and was statistically smaller than MDCs for speakers with MS (average = 10.08%, range = 5.30%-15.62%) and those for speakers with PD (average = 10.98%, range = 8.60%-13.98%). Statistical analyses further revealed significant differences between MDCs across severity categories. Conclusions: In agreement with previous work in ALS conducted under similar conditions (i.e., orthographic transcription of SIT sentences in a quiet listening environment), the MDC[subscript 95] of speech intelligibility ranged from 3% to 10% for speakers with MS and PD who have mildly impaired speech. These estimates are a step toward the development of a universal language with which to evaluate speech changes in a variety of patient populations.