Much of the fruit fly genome is compact ("Escherichia coli mode"), indicating a genome-wide selection pressure against DNA with little adaptive function. However, in the bithorax complex (BX-C) homeodomain genes are widely dispersed with large introns ("mammalian mode"). Chargaff difference analysis of compact bacterial and viral genomes has shown that most mRNAs have the potential to form stem-loop structures with purine-rich loops. Thus, for many taxa if transcription is to the right, the top (mRNA synonymous) DNA strand has purine-rich loop potential, and if transcription is to the left, the top (template) strand has pyrimidine-rich loop potential. The best indicator bases for transcription direction are A and T for AT-rich genomes, and C and G for CG-rich genomes. Consistent with this, Chargaff difference analysis of BX-C genes and several non-BX-C genes shows that, whatever the mode, mRNAs have the potential to form stem-loop structures with A-rich loops. We confirm that many potential open reading frames in the BX-C are unlikely to be functional. Conversely, we suggest that a few unassigned open reading frames may actually be functional. Since apparent organization in the mammalian mode cannot be explained in terms of unacknowledged open reading frames, yet the fruit fly genome is under pressure to be compact, it is likely that many BX-C functions do not involve the encoding of proteins.