Emotional self-regulation plays a pivotal role in socialization and moral development. This capacity critically depends on the development of the prefrontal cortex (PFC). The present functional magnetic resonance imaging study was conducted to identify the neural circuitry underlying voluntary self-regulation of sadness in healthy girls (aged 8-10). A 2 x 2 factorial design was implemented with Emotion (No Sadness vs. Sadness) and Regulation (No Reappraisal vs. Reappraisal) as factors. In the No Reappraisal conditions, subjects were instructed to react normally to neutral and sad film excerpts whereas in the Reappraisal conditions, subjects were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. A significant interaction of the Emotion and Regulation factors revealed that reappraisal of sad film excerpts was associated with bilateral activations of the lateral PFC (LPFC; Brodmann areas [BA] 9 and 10), orbitofrontal cortex (OFC; BA 11), and medial PFC (BA 9 and 10). Significant loci of activations were also detected in the right anterior cingulate cortex (BA 24/32) and right ventrolateral PFC (BA 47). In an identical study previously conducted by our group in adult women [Biol Psychiatry 53 (2003) 502], reappraisal of sad film excerpts was associated with activation of the right OFC (BA 11) and right LPFC (BA 9). The greater number of prefrontal loci of activation found in children relative to adults during voluntary self-regulation of sadness may be related to the immaturity of the prefronto-limbic connections in childhood.