Bhattacharya et al. (Bhattacharya, A., Sudha, S., Chandra, H. S. and Steward, R. (1999) Development 126, 5485-5493) reported that loss-of-function mutations in the flex (female-specific lethal on X) gene caused female-specific lethality because flex(+) acts as a positive regulator of the master switch gene Sex lethal (Sxl). Sxl is essential for female development. Key to their conclusion was the ability of flex mutations to suppress the male lethality caused by Sxl(M) mutations, which inappropriately activate Sxl female-specific expression. Here we report our contrary findings that flex mutations fail to suppress even the weakest Sxl(M )alleles, arguing against the proposed regulatory relationship between flex and Sxl. Instead we show that the lethal flex phenotype depends on the absence of a Y chromosome, not on the presence of two X chromosomes. flex lethality is caused by a defect in the functioning of the X-linked rDNA locus called bobbed, since this defect is complemented by the corresponding wild-type rDNA complex on the Y.