SUMMARY: The history, replication, genetics, characteristics (both biological and physical), and factors involved in the pathogenesis ofMycoplasma genitaliumare presented. The latter factors include adhesion, the influence of hormones, motility, possible toxin production, and immunological responses. The preferred site of colonization, together with current detection procedures, mainly by PCR technology, is discussed. The relationships betweenM. genitaliumand various diseases are highlighted. These diseases include acute and chronic nongonococcal urethritis, balanoposthitis, chronic prostatitis, and acute epididymitis in men and urethritis, bacterial vaginosis, vaginitis, cervicitis, pelvic inflammatory disease, and reproductive disease in women. A causative relationship, or otherwise strong association, between several of these diseases andM. genitaliumis apparent, and the extent of this, on a subjective basis, is presented; also provided is a comparison betweenM. genitaliumand two other genital tract-orientated mollicutes, namely,Mycoplasma hominis, the first mycoplasma of human origin to be discovered, andUreaplasmaspecies. Also discussed is the relationship betweenM. genitaliumand infertility and also arthritis in both men and women, as is infection in homosexual and immunodeficient patients. Decreased immunity, as in HIV infections, may enhance mycoplasmal detection and increase disease severity. Finally, aspects of the antimicrobial susceptibility and resistance ofM. genitalium, together with the treatment and possible prevention of mycoplasmal disease, are discussed.