Empathizing and systemizing have recently been put forward as two important individual-difference dimensions, whose different mean levels in men and women are argued to account for many psychological sex differences. This paper presents a series of studies designed to investigate the reliability and validity of the empathizing and systemizing quotients (EQ & SQ), to relate them to existing personality constructs, and to replicate reported sex and sexual orientation-related differences. Correlations with interests and social behaviour suggest the two measures are valid. However, empathizing appears essentially equivalent to agreeableness in the five-factor model of personality. Systemizing cannot be reduced to established personality dimensions, though it is moderately correlated with conscientiousness and openness. Men have higher levels of systemizing than women, and non-heterosexual women higher than heterosexuals. However, no differences were found between heterosexual and non-heterosexual men. Although systemizing and empathizing account for a number of observed sex differences, there are others they do not explain.