The book drew a negative reaction from psychoanalysts, who criticized Tripp's dismissive treatment of psychoanalytic theories, accused him of being biased in favor of homosexuality, charged that he mistakenly claimed that gay men tend to have a larger than average penis size, and objected to his discussion of attempts to change homosexuality through psychotherapy.

[5] According to the writer Paul Moor, the psychoanalyst Irving Bieber filed an ethics complaint against Tripp with the American Psychological Association.

[12] Authors who have complimented aspects of The Homosexual Matrix include the anthropologist Donald Symons,[13] the philosopher Timothy F. Murphy,[14] the queer theorist David M. Halperin,[15] and the journalist Philip Nobile.

[10] However, the historian of science Brian Easlea considered it regrettable that Tripp did not further explore the way in which male sexual attraction depends on motifs of dominance.

[17][18] The psychiatrist Ruth Tiffany Barnhouse maintained that while The Homosexual Matrix had been praised for its avoidance of bias, it contains multiple misrepresentations.

She criticized Tripp's understanding of masculinity, relations between the sexes, and sexual attraction, as well as his use of the term "inversion", noting that it differs from that originally employed by psychiatrists.

"[17] The social theorist Jonathan Dollimore described Tripp's account of psychoanalytic theories of homosexuality as an over-simplification bordering on parody.

[19] The geneticist Dean Hamer credited Tripp with providing the clearest articulation of the social learning theory of sexual orientation.

However, he found the theory itself implausible, and rejected it on numerous grounds, arguing that it is inconsistent with anthropological evidence and human evolutionary history, and fails to explain the existence of homosexuality.

[22] Fluckiger called the book "easily the most provocative work on sexuality to have appeared in a long time" and credited Tripp with offering a powerful challenge to established views about homosexuality and showing command of a range of data from many fields.

[27] Lynch wrote that while initially delighted by the work, he later concluded that it was a "deceptive book inadequate to its task" that the gay movement should not endorse.

He argued that Tripp's understanding of sexual relations between men and women, and his account of how tension between the sexes creates erotic excitement, were influenced by biological determinism.

[28] Lynch subsequently wrote that the book had been criticized for Tripp's failure to discuss the gay rights movement and negative view of women.

[34] Derbyshire dismissed the book, arguing that it was based in "bourgeois social science" and that Tripp did not appreciate the role of sexism in supporting taboos against homosexuality, which he viewed through "the ideological forms of advanced capitalism" and therefore misunderstood as a "unitary and trans-historical category".

She described Tripp's model of heterosexual relations as sexist, criticized him for focusing only on male homosexuality, and noted that he barely mentioned the gay liberation movement.

He wrote that Tripp's conclusion that homosexuality is not related to fear or anger toward women, family relationships, or a reflection of confusion over sexual identity, was baseless.

He accused Tripp of trying to normalize or exalt homosexuality and denigrate heterosexuality and women, and those who endorsed his work of politicizing sex research.