Neuroimaging studies have indicated that persistent developmental stuttering (PDS) may be associated both with an abnormality in white matter of left-hemispheric speech areas and a right-hemispheric hyperactivity. The latter may compensate for the deficient structural connectivity in the left hemisphere. To investigate the effects of stuttering therapy on brain activity nine male adults with PDS underwent functional magnetic resonance imaging (fMRI) before and within 12 weeks after fluency shaping therapy. Brain response differences during overt sentence reading before and after therapy were assessed by utilizing random effects analyses. After therapy, a more widespread activation was observed in frontal speech and language regions and temporal areas of both hemispheres, particularly and more pronounced on the left side. Interestingly, distinct posttreatment left-sided activation increases were located directly adjacent to a recently detected area of white matter anomaly [M. Sommer, M.A. Koch, W. Paulus, C. Weiller, C. Buchel (2002). Disconnection of speech-relevant brain areas in persistent developmental stuttering. "The Lancet," 360, 380-383] suggesting that fluency shaping techniques reorganize neuronal communication between left-sided speech motor planning, motor execution, and temporal areas. Hence, a therapeutic mechanism can be assumed to remodel brain circuitry close to the source of the dysfunction instead of reinforcing compensation via homologous contralateral brain networks. Educational objectives: The reader will learn about and be able to: (1) describe brain activation changes detected shortly after fluency-shaping therapy; (2) identify left-hemispheric regions where a (re)functionalization after fluency-shaping therapy seems to occur adjacent to a recently described abnormal white matter region in PDS subjects; and (3) discuss how an effective cerebral compensation mechanism for stuttering could work. (Contains 2 figures and 1 table.)