Background: There is a need for exercise strategies that maximize motor function and related changes in the central nervous system for people with progressive multiple sclerosis (MS). While intensive motor rehabilitation approaches appear to hold promise, it is possible that prior exposure to less intensive exercise programming could prepare individuals for the demands of intensive training and augment rehabilitation response. Objectives: To explore the successive effects of non-intensive exercise and intensive task-oriented rehabilitation on motor function and corticospinal excitability in individuals with progressive MS. Methods: Two participants with progressive MS completed an 8-week non-intensive, aerobic and resistance exercise program (3 hours/week), followed by a 4-week intensive task-oriented rehabilitation program targeting walking and balance (6 hours/week). Clinical assessments were performed at baseline (BL), and after each program (POST-1, POST-2, respectively). Transcranial magnetic stimulation (TMS) examined excitability of corticospinal pathways projecting to the less-affected tibialis anterior (TA) and first dorsal interosseous (FDI) muscles. Interviews characterized program acceptability and perceived impact. One-month follow-up assessments are pending. Results: Participant 1. 65-year old male, primary progressive MS, Patient Determined Disease Steps (PDDS) score of 5, physically active at baseline. Timed 25-foot Walk Test (T25-FW) improved from 7.5 s (BL), to 6.7 s (POST-1), to 5.9 s (POST-2). Berg Balance Short Form (BB-SF) scores were 16/28 (BL), 18/28 (POST-1), and 18/28 (POST-2). Average amplitude of motor evoked potentials (MEPs) at 120% active motor threshold (aMT) for TA were 0.38 mV (BL), 0.28 mV (POST-1), and 0.48 mV (POST-2), and for FDI were 2.02 mV (BL), 1.97 mV (POST-1), and 1.17 mV (POST-2). Participant 2. 57-year old female, secondary progressive MS, PDDS score of 5, not physically active at baseline. T25-FW improved from 25.1 s (BL), to 19.3 s (POST-1), to 12.8 s (POST-2). BB-SF score changed from 10/28 (BL), to 12/28 (POST-1), to 20/28 (POST-2). MEPs could not be elicited for the TA at any time point. Average MEP amplitude at 120% aMT for FDI were 0.71 mV (BL), 0.49 mV (POST-1), and 0.90 mV (POST-2). Programs were perceived as acceptable and beneficial, with intensive programming considered acceptable for four weeks or less. Non-intensive exercise prior to intensive task-oriented rehabilitation was perceived as a facilitator of success. Conclusions: Participants achieved clinically important gains (>20%) in walking speed over the study period. Improvements in Participant 2, who was not physically active at baseline, were striking and appeared to be amplified by intensive, task-oriented rehabilitation. Changes in corticospinal excitability were variable but increases may be limited to muscles targeted by intensive training.