The 2.2 kb mRNA of the Dictyostelium discoideum prespore gene EB4-PSV is constitutively transcribed during growth and development, but the message is only accumulated when cells form aggregates and establish the prespore-prestalk pattern. Disruption of the pattern by mechanical disaggregation results in a rapid loss of the mRNA, while transcription remains nearly unchanged. In early development and after disaggregation, when the mRNA is unstable, a 1.8 kb antisense transcript originating from the same gene locus is detected. This RNA has apparently no coding capacity and is transcriptionally regulated by a promoter located within the translated region of the gene. Excess transcription of antisense RNA in vegetative cells and after disaggregation suggests its involvement in the control of mRNA stability. In agreement with this assumption, the inhibition of RNA synthesis during disaggregation prevents destabilization of the mRNA. This stability regulation of an endogenous mRNA is reminiscent of the loss of specific mRNAs in cells transformed with antisense constructs.