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We develop models of the rates of evolution at sex-linked and autosomal loci and of the rates of fixation of chromosomal rearrangements involving sex chromosomes and autosomes. We show that the substitution of selectively favorable mutations often proceeds more rapidly for X- or Y-linked loci than for the autosomes, provided that mutations are recessive or partially recessive on the average. Selection acting on a quantitative character is expected to result in similar long-term rates of gene substitution for X-linked and autosomal loci, unless there is strong directional dominance. Short-term responses to such selection often preferentially fix alleles at autosomal loci. The fixation of slightly deleterious alleles by random drift and the stochastic turnover of alleles at loci controlling quantitative characters under stabilizing selection usually proceed somewhat more slowly at sex-linked loci. In contrast, the fixation of underdominant chromosomal rearrangements by random genetic drift is faster with sex linkage. Sex-specific selection may also differentially favor the fixation of sex-linked rearrangements. These results are discussed in relation to genetic and cytological data on species differences. We show that the frequently disproportionate effects of the sex chromosomes on interspecific inviability or sterility are consistent with the hypothesis that the gene differences concerned involve recessive or partially recessive alleles fixed by selection. Haldane's rule is readily interpreted in this light. There is little evidence for strong effects of the sex chromosomes on quantitative characters in interspecific crosses, in accordance with our theoretical results. Thus, the evolution of reproductive isolation may not be the byproduct of selective change in additively inherited, polygenic traits. Rather, it may be due mainly to the fixation of favorable mutations whose effects on fitness reflect locus-specific effects on the phenotype. These mutations behave as major genes in the sense of contributing the bulk of the genetic variance in the characters that they control during the course of the mutations' substitution. The data on the genetics of short-term responses to selection in Drosophila are hard to interpret, but, in accordance with theory, these responses do not usually seem to involve the X chromosome disproportionately. In some groups, there is evidence for a disproportionate role of the sex chromosomes in chromosomal changes, but others show no clear pattern. Factors that may distort the expectations of the simple models of chromosomal evolution are discussed.