One hundred and five healthy nonimmunes in Colombia took part in a randomize, double-blind comparison of 250 mg of Lariam (L) (active ingredient: mefloquine) on alternate weeks or one tablet of Fansidar (F) (active ingredients: sulfadoxine and pyrimethamine) weekly for malaria prophylaxis during at least six months. Volunteers also gave blood for determination of drug concentrations after six months and/or 24-27 months of prophylaxis. Twenty-five volunteers withdrew involuntarily when they lost their jobs in the company. Two who took L withdrew due to moderate diarrhea and mild nausea or headache, weakness, drowsiness and anxiety. One volunteer stopped taking F due to severe unilateral hypostatic eczema and slight S-T depressions on the ECG. The rest completed at least six (range 6-36) months of prophylaxis. The mean half-life for L was 26 days. The AUCs in the time interval 0-14 days for L varied between 19.3-31.5 mumol x days/l. For the main metabolite, the corresponding range was 28.8-81.3 mumol x days/l. The range of trough concentrations at day 0 and 14 were 0.95-2.01 mumol/l for L and 1.69-5.62 mumol/l for the metabolite. No differences in tolerability and efficacy were noted between L and F. Our kinetic results do not indicate that enzymatic induction or inhibition would be important during long-term prophylaxis with mefloquine. This favors a continued use of the drug for very long periods of time (= years).