Preliminary assessment of efficacy of mefloquine/-sulphadoxine/pyrimethamine (MSP) combination in the treatment of uncomplicated Plasmodium infections was conducted in-vivo in non-immune and semi-immune children in Damboa, in the North east of Nigeria using a 7-day protocol. Six hundred and forty-six (76.4%) subjects out of 846 screened had positive Plasmodium infections. Seventy-two patients aged 6 months to 11 years were enrolled, of whom 69 (95.8%) completed the study. MSP demonstrated high clinical efficacy, producing 100% cure rate against pure P. falciparum (77.8%), pure P. malariae (18.1%) and mixed P. falciparum and P. malariae (4.2%) infections. GMPDs for P. falciparum, P. malariae and mixed infections were 4,826, 3,680 and 12,573 a sexual stages per microl of whole blood. The mean parasite clearance time (MPCT) was 4.42 days for pure P. falciparum parasitaemia and 4.82 days for P. malariae alone. No parasitologic failure occurred in the patients. Clinical response occurred rapidly; all fever cases cleared within 24 hours. Moreover, significant (P<0.05) PCV improvement occurred in 7 days from an average of 33.8 +/- 4.5% on D0 to 35.5 +/- 3.5% on D7. Besides, this drug was well tolerated by majority of patients. Details of these findings are presented and discussed against the background of increased efforts towards effective malaria treatment and control in Nigeria.