During sporulation, Bacillus subtilis undergoes an asymmetric division that results in two cells with different fates, the larger mother cell and the smaller forespore. The protein phosphatase SpoIIE, which is required for activation of the forespore-specific transcription factor sigma(F), is also required for optimal efficiency and timing of asymmetric division. We performed a genetic screen for spoIIE mutants that were impaired in sporulation but not sigma(F) activity and isolated a strain with the mutation spoIIEV697A. The mutant exhibited a 10- to 40-fold reduction in sporulation and a sixfold reduction in asymmetric division compared to the parent. Transcription of the sigma(F)-dependent spoIIQ promoter was increased more than 10-fold and was no longer confined to the forespore. The excessive sigma(F) activity persisted even when asymmetric division was prevented. Disruption of spoIIGB did not restore asymmetric division to the spoIIEV697A mutant, indicating that the deficiency is not a consequence of predivisional activation of the mother cell-specific transcription factor sigma(E). Deletion of the gene encoding sigma(F) (spoIIAC) restored asymmetric division; however, a mutation that dramatically reduced the number of promoters responsive to sigma(F), spoIIAC561 (spoIIACV233 M), failed to do so. This result suggests that the block is due to expression of one of the small subset of sigma(F)-dependent genes expressed in this background or to unregulated interaction of sigmaF with some other factor. Our results indicate that regulation of SpoIIE plays a critical role in coupling asymmetric division to sigma(F) activation in order to ensure proper spatial and temporal expression of forespore-specific genes.