Sex differences in gene expression have been widely studied in Drosophila melanogaster. Sexually dimorphic expression varies across strains, but many molecular studies of regulation have focused on only a single strain or on genes that show robust sexually dimorphic expression in many strains. How extensive variability is across strains and whether this variability occurs among genes regulated directly by sex determination genes is unknown. To address these questions, we examine differences between strains in sexually dimorphic gene expression in Drosophila adult head tissues. We also examine gene expression in doublesex mutants to determine whether a gene with sex-differential expression is regulated by DSX isoforms and the mode by which DSX regulation produces sex-differential expression. The best known mode of DSX regulation is the classic mode, in which DSX represses in one sex and activates in the other. However, there are multiple additional ways in which DSX regulation can produce sex-differential expression and we examine all possible modes in this study. Our results show that there is substantial flexibility in somatic regulation of sex-differential expression. The sets of genes with sexually dimorphic expression in each strain show remarkably little overlap. The presence and prevalence of different DSX modes also varies between strains, with large differences in the prevalence of different modes among genes with female biased expression. Despite these differences, the genes identified as regulated by DSX by analysis of doublesex mutations are enriched in each strain for known sites of DSX occupancy in the genome. Neither the observation of DSX binding in a gene’s regulatory regions nor the specific mode of DSX regulation explain why some genes show robust sex-differential expression, while others differ between strains. Thus, regulation by DSX, does not appear to confer a robust pattern of expression with respect to strain differences. Finally, we find that in adult head tissues sex-biased genes in general are enriched on the X and highly enriched on the fourth chromosome in both strains and that the fourth chromosome is more specifically enriched with regions that are occupied by DSX isoforms. Overall these results provide insights into a more complete pool of potential DSX targets within the genome, as well as the molecular flexibility of DSX regulation.