The efficacy of chloroquine for treating uncomplicated Plasmodium falciparum malaria was evaluated in 98 children in Nigeria. Forty-three children failed chloroquine treatment (21 RI, 20 RII, 2 RIII) and were allocated at random to receive multiple doses of a combination of chloroquine and chlorpheniramine or a single dose of mefloquine orally. The parasite and fever clearance times were 2.7 +/- 1.0 d and 1.6 +/- 0.6 d, respectively, in children treated with the combination and 1.6 +/- 0.5 d and 1.1 +/- 0.3 d, respectively, for mefloquine treatment. The cure rate on day 14 was 81% among children receiving chloroquine/chlorpheniramine and 100% on days 14 and 28 with mefloquine. Three children who failed treatment with the combination responded promptly to mefloquine, with clearance of parasitaemia and fever within 48 h. Adverse effects following therapy were minimal, comprising drowsiness and pruritus in the combination group and abdominal discomfort in the mefloquine group. Isolates obtained from children who failed initial treatment with chloroquine were resistant to chloroquine but sensitive to mefloquine in vitro. The efficacy of this combination of chloroquine and chlorpheniramine confirmed previous reports of enhanced activity and it was effective in the management of mild to moderate chloroquine-resistant malaria. Although mefloquine is more effective in this respect, the combination, when developed, will be a valuable addition to the list of drugs for the management of chloroquine-resistant malaria.