We report a Mexican family in which two sibs were identified as ''clas
sic'' XX males without genital ambiguities. Molecular studies revealed
that both patients were negative for several Y sequences, including S
RY. A review of familial cases disclosed that this is the first family
where a complete male phenotype was observed in Y-negative XX male no
n-twin brothers. These data suggest that an inherited loss-of-function
mutation, in a gene participating in the sex-determining cascade, can
induce normal male sexual differentiation in the absence of SRY.