While the incidence of cryptococccal meningitis in thedeveloped world has declined with widespread, earlyantiretroviraltherapy(ART),cryptococcaldiseaseremainsa major opportunistic infection and leading cause ofmortality in patients infected with HIV in much of thedeveloping world. Most HIV-related cases are caused byCryptococcus neoformans var. grubii (serotype A), while var.neoformans (serotype D) is responsible for a proportion,especially in Europe, and there are a small number ofCryptococcus gatti infections (formerly C. neoformansserotypes B and C) [1,2]. The last includes a small numberof cases in HIV-infected individuals forming part of anunprecedented outbreak of C. gattii infections, predomi-nantly in apparently immunocompetent patients, onVancouver Island, Canada [3,4].C. neoformans is distributed worldwide. An ubiquitousenvironmental saphrophyte, it is found in soil contami-nated with pigeon droppings and has also been isolatedfrom the heartwood of several tree species in SouthAmerica [5] and India [6], and from the homes of AfricanHIV-seropositivepatients[7,8].Exposuremaybecommon[9], although the exact circumstances are usually unclear.Inhalation of small, thinly encapsulated yeasts, orbasidiospores [10], may lead to an initial pulmonaryinfection,which,dependingonhostimmuneresponseandthe number and virulence of the organisms, is cleared,contained within granulomata as a latent infection ordisseminates. The minority in whom disease disseminatestypically have defects in T cell function, throughmalignancy,immunosuppressivemedication,autoimmunedisease or sarcoidosis [11,12] or HIV infection, indicatingthe role of T cell-mediated immunity in host defence.In HIV-seropositive patients, most episodes of crypto-coccalmeningitisprobablyrepresentreactivationoflatentinfection, which may have been acquired many yearsearlier. There is compelling evidence for latent infectionin a rat model [13] and humans [14]. Dromer andcolleagues [15] typed C. neoformans isolates from HIV-seropositive patients diagnosed with cryptococcosis inFrance, some of whom were from Africa but had lived inFrance for a median of over 9 years. There was asignificant clustering of isolates from African comparedwith European patients, suggesting that the patients hadacquired their isolates long before the development ofclinical disease. A proportion of HIV-related cases,however, may result from dissemination of new orprimary infection [16], as has been observed in the recentoutbreak of C. gattii infection in British Columbia [17].HIV-associatedcryptococcalmeningitisusuallypresentsasa subacute meningo-encephalitis in profoundly immuno-suppressedpatients(CD4cellcounts<100cells/ml), withmalaise, headache, fever and, later, visual disturbance andaltered mental status. Signs, if present, may includemeningism, papilloedema, cranial nerve palsies [particu-larly sixth nerve palsies reflective of raised pressure incerebrospinal fluid (CSF)] and reduced conscious level.The diagnosis is usually straightforward. The highorganism load in this setting means the sensitivity of Indiaink staining of CSF is high. Those who have a negative