From July 1987 to June 1988 a randomized, double-blind, comparative placebo-controlled field trial was conducted in a group of villages near Ibadan, Nigeria. The aim of the study was to assess the suppressive tolerability and efficacy of four antimalarials (Fansimef, Lariam, Fansidar, chloroquine) given for 24 weeks. Fansimef and Lariam were given with loading and maintenance doses, Fansidar and chloroquine as one tablet per week for 24 weeks. Of 567 enrolled subjects, 114 (20%) had parasitaemia on entry. Eight episodes of symptomatic falciparum malaria occurred during the trial, seven in the placebo group, and one in the Fansimef group. Compared with placebo, parasitaemia was effectively suppressed by all four drug regimens. Adverse event data were not significantly different between groups: six adverse events per 114 participants in the Fansimef group, six/113 in the mefloquine group, five/111 in the Fansidar group, 17/115 in the chloroquine group and eight/114 in the placebo group. Safety of Fansimef for 24 weeks in endemic areas was comparable for standard antimalarials in this trial and provides support for the use of this drug for the treatment of resistant malaria in indigenous African populations.