The formation of a testis from the indifferent gonad is the prelude to sequential steps in male sex differentiation orchestrated by time-dependent androgen biosynthesis and action. Information about the cellular and molecular mechanisms of androgen action can be obtained by the study of disorders of sex differentiation in males. The pivotal role of the androgen receptor as a ligand-induced transcription factor is emphasised and preliminary studies are described which attempt to identify developmentally regulated androgen-responsive genes. That androgen action can be modulated by gene polymorphisms is illustrated by the influence of an androgen receptor polyglutamine repeat in the multi-factorial causation of less severe forms of male under-masculinization.