We used a convenient quantitative dot blot assay to measure transcript levels for two X chromosomelinked genes, myo-2 and act4, in the nematode Caenorhabditis elegans. We show that there is dosage compensation of transcript levels for these two genes between XX herm.aphrodites and XO males and that a mutation in the dpy-21 gene, postulated from genetic analysis to be involved in control of X chromosome expression, can affect these transcript levels in the manner predicted. However, we observe the dpy-21 effects only at some stages of the life cycle and not at others. These results are generally consistent with earlier genetic and molecular evidence.In many animals one sex has two X chromosomes and the other sex only one. Despite this 2-fold difference in X chromosome dosage, most X-linked mutations cause similar mutant phenotypes in both sexes (1), and both sexes show equivalent levels of activities for many enzymes encoded by X-linked genes (2, 3). The mechanism of X chromosome dosage compensation responsible for this equivalence varies among different organisms. In mammals, it is accomplished by inactivation of one of the two X chromosomes in females during most of the life cycle (reviewed in ref. 2). In the fruit fly Drosophila, both X chromosomes are expressed in XX females, and compensation occurs by hyperactivation (relative to the autosomes) of the single X in XY males (reviewed in ref.3).The nematode Caenorhabditis elegans has two sexes: self-fertilizing hermaphrodites, which have two X chromosomes (XX), and males, which have one X chromosome (X0). There is no Y chromosome; the primary signal for sex determination is the X/A ratio, the ratio of X chromosomes to sets of autosomes (4). Early evidence for dosage compensation in C. elegans was genetic, based on analysis of hypomorphic mutations in X-linked genes. These are mutations causing partial loss of function such that the resulting phenotype varies with the level of the mutant gene product. Hypomorphic mutations of X-linked genes in C. elegans are observed to cause similar phenotypes in XX and X0 animals, indicating similar levels of the corresponding gene products, and thereby providing evidence for some mechanism of compensation for the difference in X chromosome dosage (5,6).To achieve dosage compensation, the level of X chromosome expression must presumably be dictated by the X/A ratio, but the genetic basis for this regulation is still unclear. At least four autosomal and two X-linked loci have been identified as possible-regulators of X chromosome expression. The phenotypes resulting from mutations in these genes are dependent on the X/A ratio in the mutant animal (7). These mutations result in the short phenotype known as dumpy (Dpy). Such X/A-dependent dpy genes can be grouped into two classes. Genes in the first class, all autosomal, are dpy-21 V (7), dpy-26 IV (7), dpy-27III (8), and dpy-28 III (9). Recessive mutations in dpy-21 and dpy-26 cause an increase in X expression based on the observation that they suppress the phenotypes re...