The in vivo sensitivity of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine was evaluated in children under 5 years of age in two areas of southern Nigeria in 1987. A modification of the WHO Standard Field and Extended Tests (in vivo) was used, with follow-up on days, 2, 3, 7, and 14 after treatment with 25 mg chloroquine per kg body weight given over 3 days, or with standard doses of sulfadoxine/pyrimethamine. Clinical and parasitological evaluations were performed. At Igbo Ora, in Oyo State, where by day 7 chloroquine was clinically successful in 94.4% of 36 children and sulfadoxine/pyrimethamine in 91.7% of 36 children, there were no parasitological failures in either treatment group. Fever regressed significantly more rapidly with chloroquine than with sulfadoxine/pyrimethamine. At Oban, in Cross River State, initial parasite densities decreased markedly with the chloroquine regimen but 63.6% of 44 children were parasitological failures on days 3, 7, or 14; and all of the 26 children who failed parasitologically and completed follow-up were successfully treated with sulfadoxine/pyrimethamine. By day 7, clinical success was demonstrated for 77.3% of the children treated with chloroquine. The in vitro sensitivity to chloroquine, quinine, and mefloquine at Igbo Ora indicated that isolates of P. falciparum were sensitive to chloroquine and quinine, but had reduced sensitivity to mefloquine. Because of its continued clinical efficacy, chloroquine remains the recommended treatment for children with uncomplicated malaria in Nigeria. Health providers are, however, encouraged to maintain supplies of sulfadoxine/pyrimethamine as an alternative and to refer patients promptly if necessary.