CGP 56697 (Riamet(TM)) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4x4 tablets over 48 h, was compared to halofantrine, given as 3x2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n=51) or halofantrine (n=52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P<0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P<0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P=0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (>30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptably high (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days. Copyright (C) 1999 Elsevier Science B.V.