One important role of DIF, the stalk cell-specific inducer of Dictyostelium, may be to divert cells from the spore cell pathway of differentiation. The D19 gene encodes an mRNA which is highly enriched in prespore over prestalk cells in the migratory slug. We show, using a mutant defective in DIF accumulation, that the concentration of D19, and several other prespore mRNA sequences, decreases in the presence of exogenous DIF. There is evidence that both transcriptional and post-transcriptional controls operate to regulate expression of these genes. We have performed in vitro nuclear transcription and mRNA half-life analyses, and find that DIF acts at the transcriptional level to repress the accumulation of the D19 mRNA.