Mefloquine is an orally administered blood schizontocide for the chemoprophylaxis of malaria in nonimmune travelers. New pharmacokinetic data has shown that food increases the bioavailability of mefloquine. Steady-state pharmacokinetics of weekly prophylaxis in long term travelers have shown that toxic accumulation does not occur and that weekly dosing is associated with protective levels of the drug. The pharmacokinetics of mefloquine are highly stereospecific and all pharmacokinetic parameters, except tmax are significantly different for the (+) and (-) enantiomers. Mefloquine and its metabolite are not appreciably removed by hemodialysis. Steady-state levels of mefloquine can be attained in a reduced time frame of 4 days compared to 7-9 weeks using a loading dose strategy of 250 mg mefloquine daily for 3 days followed thereafter by weekly mefloquine dosage. This strategy, is however, associated with a higher incidence of an adverse event (AE). Cumulative evidence suggests a high protective efficacy of mefloquine (>91%) in nonimmune travelers to areas of chloroquine resistant Plasmodium falciparum (CRPF) except for clearly defined regions of multi-drug resistance. Reports from sub-Saharan Africa indicate a low but increasing level of resistance to this drug. Mefloquine resistance is associated with halofantrine and quinine resistance but not with chloroquine resistance. Penfluridol has been shown to reverse P. falciparum mefloquine resistance in vitro. There is some controversy regarding the tolerabilty of mefloquine for malaria chemoprophylaxis. A review of the studies conducted during 1992-1998 shows that in the reporting of any AE the incidence lies in the range (12-90%) and where there is a comparator, is equivalent to the incidence reported for almost all alternative regimens. When some measure of subjective severity is applied to the rating of AE, it appears that 11-17% of travelers are, to some extent, incapacitated by AE. Major studies and worldwide monitoring have shown that serious events are rare. A recent meta-analysis showed that rates of withdrawal and overall incidence of AE with mefloquine were not significantly higher than those observed with comparator regimens except that mefloquine was more likely to cause insomnia and fatigue. Withdrawals in mefloquine arms were higher than in placebo arms. No performance deficit or functional impairment was observed in five clinical toxicity studies of mefloquine prophylaxis, including a study of driving performance. There is limited data regarding use of mefloquine in pregnancy. Early animal studies have documented teratogenic and embryotoxic effects associated with the use of high dose mefloquine. Two studies have shown a relatively high incidence of spontaneous abortions in mefloquine users. Cumulative evidence, however, is reassuring and has led the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) to sanction the use of mefloquine in pregnant women during the second and third trimesters. In conclusion, mefloquine prophylaxis is recommended for travelers to high risk areas of chloroquine resistant Plasmodium falciparum. The risk of malarial infection and the proven efficacy of mefloquine to prevent malaria should be weighed against the risk of drug associated adverse events.